2,744
Views
2
CrossRef citations to date
0
Altmetric
signature reviews

Pathogenicity & virulence of Histoplasma capsulatum - A multifaceted organism adapted to intracellular environments

, , , & ORCID Icon
Article: 2137987 | Received 18 May 2022, Accepted 14 Oct 2022, Published online: 26 Oct 2022

References

  • Mittal J, Ponce MG, Gendlina I, et al. Histoplasma capsulatum: mechanisms for pathogenesis. Curr Top Microbiol Immunol. 2019;422:1900–1919.
  • Wheat LJ, Azar MM, Bahr NC, et al. Histoplasmosis. Infect Dis Clin North Am. 2016;30(1):207–227. DOI:10.1016/j.idc.2015.10.009
  • Knox KS, Hage CA. Histoplasmosis. Proc Am Thorac Soc. 2010;7(3):169–172.
  • Sacco M, Maresca B, Kumar BV, et al. Temperature- and cyclic nucleotide-induced phase transitions of Histoplasma capsulatum. J Bacteriol. 1981;146:117–120.
  • Sacco M, Medoff G, Lambowitz AM, et al. Sulfhydryl induced respiratory ”shunt” pathways and their role in morphogenesis in the fungus, Histoplasma capsulatum. J Biol Chem. 1983;258:8223–8230.
  • Nemecek JC, Wüthrich M, Klein BS. Global control of dimorphism and virulence in fungi. Science. 2006;312:583–588.
  • Inglis DO, Voorhies M, Hocking Murray DR, et al. Comparative transcriptomics of infectious spores from the fungal pathogen Histoplasma capsulatum reveals a core set of transcripts that specify infectious and pathogenic states. Eukaryot Cell. 2013;12:828–852.
  • Beyhan S, Gutierrez M, Voorhies M, et al. A temperature-responsive network links cell shape and virulence traits in a primary fungal pathogen. PLoS Biol. 2013;11:e1001614.
  • Edwards JA, Chen C, Kemski MM, et al. Histoplasma yeast and mycelial transcriptomes reveal pathogenic-phase and lineage-specific gene expression profiles. BMC Genomics. 2013;14:695.
  • McCormack FX, Gibbons R, Ward SR, et al. Macrophage-independent fungicidal action of the pulmonary collectins. J Biol Chem. 2003;278:36250–36256.
  • Carreto-Binaghi LE, Aliouat EM, Taylor ML. Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response. Respir Res. 2016;17:66.
  • Gomez FJ, Allendoerfer R, Deepe GS. Vaccination with recombinant heat shock protein 60 from Histoplasma capsulatum protects mice against pulmonary histoplasmosis. Infect Immun. 1995;63:2587–2595.
  • Long KH, Gomez FJ, Morris RE, et al. Identification of heat shock protein 60 as the ligand on Histoplasma capsulatum that mediates binding to CD18 receptors on human macrophages. J Immunol Baltim Md. 2003;170:487–494.
  • Guimarães AJ, Frases S, Gomez FJ, et al. Monoclonal antibodies to heat shock protein 60 alter the pathogenesis of Histoplasma capsulatum. Infect Immun. 2009;77:1357–1367.
  • Guimarães AJ, Nakayasu ES, Sobreira TJ, et al. Histoplasma capsulatum heat-shock 60 orchestrates the adaptation of the fungus to temperature stress. PLoS One. 2011;6:e14660.
  • Guimarães AJ, Frases S, Pontes B, et al. Agglutination of Histoplasma capsulatum by IgG monoclonal antibodies against Hsp60 impacts macrophage effector functions. Infect Immun. 2011;79:918–927.
  • Rappleye CA, Eissenberg LG, Goldman WE. Histoplasma capsulatum alpha-(1,3)-glucan blocks innate immune recognition by the beta-glucan receptor. Proc Natl Acad Sci U S A. 2007;104:1366–1370.
  • Garfoot AL, Rappleye CA. Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis. FEBS J. 2016;283:619–633.
  • Ray SC, Rappleye CA. Flying under the radar: Histoplasma capsulatum avoidance of innate immune recognition. Semin Cell Dev Biol. 2019;89:91–98.
  • Garfoot AL, Dearing KL, VanSchoiack AD, et al. Eng1 and Exg8 are the major β-glucanases secreted by the fungal pathogen Histoplasma capsulatum. J Biol Chem. 2017;292:4801–4810.
  • Holbrook ED, Edwards JA, Youseff BH, et al. Definition of the extracellular proteome of pathogenic-phase Histoplasma capsulatum. J Proteome Res. 2011;10:1929–1943.
  • Youseff BH, Holbrook ED, Smolnycki KA, et al. Extracellular superoxide dismutase protects histoplasma yeast cells from host-derived oxidative stress. PLoS Pathog. 2012;8:e1002713.
  • Holbrook ED, Smolnycki KA, Youseff BH, et al. Redundant catalases detoxify phagocyte reactive oxygen and facilitate Histoplasma capsulatum pathogenesis. Infect Immun. 2013;81:2334–2346.
  • Isaac DT, Berkes CA, English BC, et al. Macrophage cell death and transcriptional response are actively triggered by the fungal virulence factor Cbp1 during H. capsulatum infection. Mol Microbiol. 2015;98:910–929.
  • English BC, Van Prooyen N, Örd T, et al. The transcription factor CHOP, an effector of the integrated stress response, is required for host sensitivity to the fungal intracellular pathogen Histoplasma capsulatum. PLoS Pathog. 2017;13:e1006589.
  • Azimova D, Herrera N, Duvenage L, et al. Cbp1, a fungal virulence factor under positive selection, forms an effector complex that drives macrophage lysis. PLoS Pathog. 2022;18:e1010417.
  • Gomez FJ, Pilcher-Roberts R, Alborzi A, et al. Histoplasma capsulatum cyclophilin a mediates attachment to dendritic cell VLA-5. J Immunol. 2008;181:7106–7114.
  • Underhill DM, Rossnagle E, Lowell CA, et al. Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood. 2005;106:2543–2550.
  • Shen Q, Beucler MJ, Ray SC, et al. Macrophage activation by IFN-γ triggers restriction of phagosomal copper from intracellular pathogens. PLoS Pathog. 2018;14:e1007444.
  • Loulergue P, Bastides F, Baudouin V, et al. Literature review and case histories of Histoplasma capsulatum var. duboisii infections in HIV-infected patients. Emerg Infect Dis. 2007;13(11):1647–1652. DOI:10.3201/eid1311.070665
  • Hage CA, Knox KS, Wheat LJ. Endemic mycoses: overlooked causes of community acquired pneumonia. Respir Med. 2012;106(6):769–776.
  • Hage CA, Wheat L, Loyd J, et al. Pulmonary histoplasmosis. Semin Respir Crit Care Med. 2008;29(2):151–165. DOI:10.1055/s-2008-1063854
  • Wheat LJ, Conces D, Allen SD, et al. Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management. Semin Respir Crit Care Med. 2004;25(02):129–144. DOI:10.1055/s-2004-824898
  • Adenis A, Basurko C, Change Dufour J, et al. Tuberculosis and histoplasmosis among human immunodeficiency virus–infected patients: a comparative study. Am J Trop Med Hyg. 2014;90(2):216–223. DOI:10.4269/ajtmh.13-0084
  • Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev. 2007;20(1):115–132.
  • Tobón AM, Gómez BL. Pulmonary histoplasmosis. Mycopathologia. 2021;186:697–705.
  • Kuate MPN, Ekeng BE, Kwizera R, et al. Histoplasmosis overlapping with HIV and tuberculosis in sub-Saharan Africa: challenges and research priorities. Ther Adv Infect Dis. 2021;8:20499361211008676.
  • Köhler JR, Hube B, Puccia R, et al. Fungi that infect humans. Microbiol Spectr. 2017;5(3). DOI:10.1128/microbiolspec.FUNK-0014-2016.
  • Darling ST. A protozoön general infection producing pseudotubercles in the lungs and focal necroses in the liver, spleen and lymphnodes. J Am Med Assoc. 1906;XLVI:1283–1285.
  • Baum GL, Schwarz J. The history of histoplasmosis, 1906 to 1956. N Engl J Med. 1957;256:253–258.
  • Rodrigues AM, Beale MA, Hagen F, et al. The global epidemiology of emerging histoplasma species in recent years. Stud Mycol. 2020;97:100095.
  • Guimarães AJ, de Cerqueira MD, Nosanchuk JD. Surface architecture of Histoplasma capsulatum. Front Microbiol. 2011;2:225.
  • Kasuga T, White TJ, Koenig G, et al. Phylogeography of the fungal pathogen Histoplasma capsulatum. Mol Ecol. 2003;12:3383–3401.
  • Teixeira MM, Patané JSL, Taylor ML, et al. Worldwide phylogenetic distributions and population dynamics of the genus histoplasma. PLoS Negl Trop Dis. 2016;10:e0004732.
  • Colombo AL, Tobón A, Restrepo A, et al. Epidemiology of endemic systemic fungal infections in Latin America. Med Mycol. 2011;49:785–798.
  • Kalata KE, Osborne CC, Willis A, et al. Disseminated histoplasmosis as an aids-defining illness presenting as fever of unknown origin in an 11-year-old female. Case Rep Pediatr. 2019;2019:9417102.
  • Adenis AA, Valdes A, Cropet C, et al. Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study. Lancet Infect Dis. 2018;18:1150–1159.
  • Nacher M, Adenis A, Sambourg E, et al. Histoplasmosis or tuberculosis in HIV-infected patients in the Amazon: what should be treated first?. PLoS Negl Trop Dis. 2014;8:e3290.
  • Pan B, Chen M, Pan W, et al. Histoplasmosis: a new endemic fungal infection in China? Review and analysis of cases. Mycoses. 2013;56:212–221.
  • Norkaew T, Ohno H, Sriburee P, et al. Detection of environmental sources of Histoplasma capsulatum in Chiang Mai, Thailand, by nested PCR. Mycopathologia. 2013;176:395–402.
  • Jung EJ, Park DW, Choi J-W, et al. Chronic cavitary pulmonary histoplasmosis in a non-HIV and immunocompromised patient without overseas travel history. Yonsei Med J. 2015;56:871–874.
  • Cottle LE, Gkrania‐klotsas E, Williams HJ, et al. A multinational outbreak of histoplasmosis following a biology field trip in the Ugandan rainforest. J Travel Med. 2013;20:83–87.
  • Gumbo T, Just-Nübling G, Robertson V, et al. Clinicopathological features of cutaneous histoplasmosis in human immunodeficiency virus-infected patients in Zimbabwe. Trans R Soc Trop Med Hyg. 2001;95:635–636.
  • Lofgren SM, Kirsch EJ, Maro VP, et al. Histoplasmosis among hospitalized febrile patients in northern Tanzania. Trans R Soc Trop Med Hyg. 2012;106:504–507.
  • Oladele RO, Ayanlowo OO, Richardson MD, et al. Histoplasmosis in Africa: an emerging or a neglected disease?. PLoS Negl Trop Dis. 2018;12:e0006046.
  • Inojosa W, Rossi MC, Laurino L, et al. Progressive disseminated histoplasmosis among human immunodeficiency virus-infected patients from West-Africa: report of four imported cases in Italy. Infez Med Riv Period Eziologia Epidemiol Diagn Clin E Ter Delle Patol Infett. 2011;19:49–55.
  • Antinori S, Magni C, Nebuloni M, et al. Histoplasmosis among human immunodeficiency virus-infected people in Europe: report of 4 cases and review of the literature. Medicine (Baltimore). 2006;85:22–36.
  • Antinori S, Giacomelli A, Corbellino M, et al. Histoplasmosis diagnosed in Europe and Israel: a case report and systematic review of the literature from 2005 to 2020. J Fungi. 2021;7:481.
  • Casalini G, Giacomelli A, Ridolfo A, et al. Invasive fungal infections complicating covid-19: a narrative review. J Fungi Basel Switz. 2021;7:921.
  • Ripa M, Galli L, Poli A, et al. Secondary infections in patients hospitalized with COVID-19: incidence and predictive factors. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2021;27:451–457.
  • Khanna A, Sinha AK, Kumar P, et al. Acute localized pulmonary histoplasmosis - another bug out of COVID’s Pandora box!. Lung India off Organ Indian Chest Soc. 2022;39:91–92.
  • de Macedo PM, Freitas AD, Bártholo TP, et al. Acute pulmonary histoplasmosis following COVID-19: novel laboratorial methods aiding diagnosis. J Fungi. 2021;7:346.
  • Messina FA, Marin E, Caceres DH, et al. Coronavirus disease 2019 (COVID-19) in a patient with disseminated histoplasmosis and HIV—a case report from Argentina and literature review. J Fungi Basel Switz. 2020;6:E275.
  • Bertolini M, Mutti MF, Barletta JA, et al. COVID-19 associated with AIDS-related disseminated histoplasmosis: a case report. Int J STD AIDS. 2020;31:1222–1224.
  • Maldonado I, Elisiri ME, Fernández-Canigia L, et al. COVID-19 associated with disseminated histoplasmosis in a kidney transplant patient. Rev Argent Microbiol. 2021;S0325-7541(21):00121–8.
  • Basso RP, Poester VR, Benelli JL, et al. COVID-19-associated histoplasmosis in an aids patient. Mycopathologia. 2021;186:109–112.
  • Stasiak CES, Nigri DH, Cardoso FR, et al. Case report: incidental finding of covid-19 infection after positron emission tomography/CT imaging in a patient with a diagnosis of histoplasmosis and recurring fever. Am J Trop Med Hyg. 2021;104(5):1651–1654. DOI:10.4269/ajtmh.20-0952
  • Taylor M, Ghodasara A, Ismail A, et al. Disseminated histoplasmosis in an immunocompetent patient after Covid-19 pneumonia. Cureus. 2021;13:e17269.
  • Cafardi J, Haas D, Lamarre T, et al. Opportunistic fungal infection associated with COVID-19. Open Forum Infect Dis. 2021;8:ofab016.
  • Azar MM, Hage CA. Laboratory diagnostics for histoplasmosis. J Clin Microbiol. 2017;55:1612–1620.
  • Azar MM, Loyd JL, Relich RF, et al. Current concepts in the epidemiology, diagnosis, and management of histoplasmosis syndromes. Semin Respir Crit Care Med. 2020;41:013–030.
  • Limper AH, Knox KS, Sarosi GA, et al. An official American thoracic society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183:96–128.
  • Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the infectious diseases society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;45:807–825.
  • Newman SL, Bucher C, Rhodes J, et al. Phagocytosis of Histoplasma capsulatum yeasts and microconidia by human cultured macrophages and alveolar macrophages. cellular cytoskeleton requirement for attachment and ingestion. J Clin Invest. 1990;85:223–230.
  • Medoff G, Maresca B, Lambowitz AM, et al. Correlation between pathogenicity and temperature sensitivity in different strains of Histoplasma capsulatum. J Clin Invest. 1986;78:1638–1647.
  • Cheung SS, Kobayashi GS, Schlessinger D, et al. RNA metabolism during morphogenesis in Histoplasma capsulatum. J Gen Microbiol. 1974;82:301–307.
  • D’Souza CA, Heitman J. Conserved cAMP signaling cascades regulate fungal development and virulence. FEMS Microbiol Rev. 2001;25:349–364.
  • Maresca B, Medoff G, Schlessinger D, et al. Regulation of dimorphism in the pathogenic fungus Histoplasma capsulatum. Nature. 1977;266:447–448.
  • Maresca B, Lambowitz AM, Kumar VB, et al. Role of cysteine in regulating morphogenesis and mitochondrial activity in the dimorphic fungus Histoplasma capsulatum. Proc Natl Acad Sci U S A. 1981;78:4596–4600.
  • Medoff G, Sacco M, Maresca B, et al. Irreversible block of the mycelial-to-yeast phase transition of Histoplasma capsulatum. Science. 1986;231:476–479.
  • Holbrook ED, Rappleye CA. Histoplasma capsulatum pathogenesis: making a lifestyle switch. Curr Opin Microbiol. 2008;11:318–324.
  • Patel JB, Batanghari JW, Goldman WE. Probing the yeast phase-specific expression of the CBP1 gene in Histoplasma capsulatum. J Bacteriol. 1998;180:1786–1792.
  • Batanghari JW, Goldman WE. Calcium dependence and binding in cultures of Histoplasma capsulatum. Infect Immun. 1997;65:5257–5261.
  • Beck MR, DeKoster GT, Hambly DM, et al. Structural features responsible for the biological stability of histoplasma’s virulence factor CBP. Biochemistry. 2008;47:4427–4438.
  • Bohse ML, Woods JP. RNA interference-mediated silencing of the YPS3 gene of Histoplasma capsulatum reveals virulence defects. Infect Immun. 2007;75:2811–2817.
  • Bohse ML, Woods JP. Expression and interstrain variability of the YPS3 gene of Histoplasma capsulatum. Eukaryot Cell. 2007;6:609–615.
  • Nguyen VQ, Sil A. Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator. Proc Natl Acad Sci U S A. 2008;105:4880–4885.
  • Webster RH, Sil A. Conserved factors Ryp2 and Ryp3 control cell morphology and infectious spore formation in the fungal pathogen Histoplasma capsulatum. Proc Natl Acad Sci U S A. 2008;105:14573–14578.
  • Rodriguez L, Voorhies M, Gilmore S, et al. Opposing signaling pathways regulate morphology in response to temperature in the fungal pathogen Histoplasma capsulatum. PLoS Biol. 2019;17:e3000168.
  • Longo LVG, Ray SC, Puccia R, et al. Characterization of the APSES-family transcriptional regulators of Histoplasma capsulatum. FEMS Yeast Res. 2018;18:foy087.
  • Beyhan S, Sil A. Sensing the heat and the host: virulence determinants of Histoplasma capsulatum. Virulence. 2019;10:793–800.
  • Han S, Mallampalli RK. The role of surfactant in lung disease and host defense against pulmonary infections. Ann Am Thorac Soc. 2015;12:765–774.
  • Carreto-Binaghi LE, Tenorio EP, Morales-Villarreal FR, et al. Detection of cytokines and collectins in bronchoalveolar fluid samples of patients infected with Histoplasma capsulatum and pneumocystis jirovecii. J Fungi Basel Switz. 2021;7:938.
  • Cain JA, Deepe GS. Evolution of the primary immune response to Histoplasma capsulatum in murine lung. Infect Immun. 1998;66:1473–1481.
  • Deepe GS, Gibbons RS, Smulian AG. Histoplasma capsulatum manifests preferential invasion of phagocytic subpopulations in murine lungs. J Leukocyte Biol. 2008;84:669–678.
  • Eissenberg LG, West JL, Woods JP, et al. Infection of P388D1 macrophages and respiratory epithelial cells by Histoplasma capsulatum: selection of avirulent variants and their potential role in persistent histoplasmosis. Infect Immun. 1991;59:1639–1646.
  • Le Cabec V, Carréno S, Moisand A, et al. Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively. J Immunol Baltim Md. 2002;169:2003–2009.
  • Pitangui NS, Voltan AR, Dos Santos CT, et al. An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophages. Front Microbiol. 2015;6:1526.
  • Deepe GS, Buesing WR. Deciphering the pathways of death of Histoplasma capsulatum-infected macrophages: implications for the immunopathogenesis of early infection. J Immunol Baltim Md. 2012;188:334–344.
  • Medeiros AI, BONATO VLD, MALHEIRO A, et al. Histoplasma capsulatum inhibits apoptosis and Mac-1 expression in leucocytes. Scand J Immunol. 2002;56:392–398.
  • Bullock WE, Wright SD. Role of the adherence-promoting receptors, CR3, LFA-1, and p150,95, in binding of Histoplasma capsulatum by human macrophages. J Exp Med. 1987;165:195–210.
  • Guimarães AJ, Cerqueira MD, Zamith‐miranda D, et al. Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages. Cell Microbiol. 2019;21:e12976.
  • Souza TN, Valdez AF, Rizzo J, et al. Host cell membrane microdomains and fungal infection. Cell Microbiol. 2021;23:e13385.
  • Ruysschaert J-M, Lonez C. Role of lipid microdomains in TLR-mediated signalling. Biochim Biophys Acta. 2015;1848:1860–1867.
  • Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science. 2010;327:46–50.
  • Kerrigan AM, Brown GD. C-type lectins and phagocytosis. Immunobiology. 2009;214:562–575.
  • Netea MG, Brown GD, Kullberg BJ, et al. An integrated model of the recognition of candida albicans by the innate immune system. Nat Rev Microbiol. 2008;6:67–78.
  • Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111:927–930.
  • Lin J-S, Huang J-H, Hung L-Y, et al. Distinct roles of complement receptor 3, Dectin-1, and sialic acids in murine macrophage interaction with histoplasma yeast. J Leukocyte Biol. 2010;88:95–106.
  • Huang J-H, Lin C-Y, Wu S-Y, et al. CR3 and dectin-1 collaborate in macrophage cytokine response through association on lipid rafts and activation of Syk-JNK-AP-1 pathway. PLoS Pathog. 2015;11:e1004985.
  • Garfoot AL, Shen Q, Wüthrich M, et al. The Eng1 β-glucanase enhances histoplasma virulence by reducing β-glucan exposure. MBio. 2016;7:e01388–01315.
  • Rappleye CA, Engle JT, Goldman WE. RNA interference in Histoplasma capsulatum demonstrates a role for alpha-(1,3)-glucan in virulence. Mol Microbiol. 2004;53:153–165.
  • Sepúlveda VE, Williams CL, Goldman WE. Comparison of phylogenetically distinct histoplasma strains reveals evolutionarily divergent virulence strategies. MBio. 2014;5:e01376–14.
  • Missall TA, Lodge JK, McEwen JE. Mechanisms of resistance to oxidative and nitrosative stress: implications for fungal survival in mammalian hosts. Eukaryot Cell. 2004;3:835–846.
  • Imlay JA. Pathways of oxidative damage. Annu Rev Microbiol. 2003;57:395–418.
  • Brummer E, Kurita N, Yosihida S, et al. Fungistatic activity of human neutrophils against Histoplasma capsulatum: correlation with phagocytosis. J Infect Dis. 1991;164:158–162.
  • Kurita N, Brummer E, Yoshida S, et al. Antifungal activity of murine polymorphonuclear neutrophils against Histoplasma capsulatum. J Med Vet Mycol Bi-Mon Publ Int Soc Hum Anim Mycol. 1991;29:133–143.
  • Schaffner A, Davis CE, Schaffner T, et al. In vitro susceptibility of fungi to killing by neutrophil granulocytes discriminates between primary pathogenicity and opportunism. J Clin Invest. 1986;78:511–524.
  • Eissenberg LG, Goldman WE. Histoplasma capsulatum fails to trigger release of superoxide from macrophages. Infect Immun. 1987;55:29–34.
  • Kennedy AD, Willment J, Dorward D, et al. Dectin-1 promotes fungicidal activity of human neutrophils. Eur J Immunol. 2007;37:467–478.
  • Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J. 2005;24:1277–1286.
  • Skrzypek F, Cenci E, Pietrella D, et al. Dectin-1 is required for human dendritic cells to initiate immune response to Candida albicans through Syk activation. Microbes Infect. 2009;11:661–670.
  • Nittler MP, Hocking-Murray D, Foo CK, et al. Identification of histoplasma capsulatum transcripts induced in response to reactive nitrogen species. Mol Biol Cell. 2005;16:4792–4813.
  • Lane TE, Otero GC, Wu-Hsieh BA, et al. Expression of inducible nitric oxide synthase by stimulated macrophages correlates with their antihistoplasma activity. Infect Immun. 1994;62:1478–1479.
  • Nakamura LT, Wu-Hsieh BA, Howard DH. Recombinant murine gamma interferon stimulates macrophages of the RAW cell line to inhibit intracellular growth of Histoplasma capsulatum. Infect Immun. 1994;62:680–684.
  • Zumft WG. Cell biology and molecular basis of denitrification. Microbiol Mol Biol Rev MMBR. 1997;61:533–616.
  • Nakahara K, Tanimoto T, Hatano K, et al. Cytochrome P-450 55A1 (P-450dNIR) acts as nitric oxide reductase employing NADH as the direct electron donor. J Biol Chem. 1993;268:8350–8355.
  • Shoun H, Tanimoto T. Denitrification by the fungus fusarium oxysporum and involvement of cytochrome P-450 in the respiratory nitrite reduction. J Biol Chem. 1991;266:11078–11082.
  • Strasser JE, Newman SL, Ciraolo GM, et al. Regulation of the macrophage vacuolar ATPase and phagosome-lysosome fusion by Histoplasma capsulatum. J Immunol Baltim Md. 1999;162:6148–6154.
  • Taylor ML, Espinosa-Schoelly ME, Iturbe R, et al. Evaluation of phagolysosome fusion in acridine orange stained macrophages infected with Histoplasma capsulatum. Clin Exp Immunol. 1989;75:466–470.
  • Eissenberg LG, Goldman WE, Schlesinger PH. Histoplasma capsulatum modulates the acidification of phagolysosomes. J Exp Med. 1993;177:1605–1611.
  • Isaac DT, Coady A, Van Prooyen N, et al. The 3-hydroxy-methylglutaryl coenzyme a lyase HCL1 is required for macrophage colonization by human fungal pathogen Histoplasma capsulatum. Infect Immun. 2013;81:411–420.
  • Sebghati TS, Engle JT, Goldman WE. Intracellular parasitism by Histoplasma capsulatum: fungal virulence and calcium dependence. Science. 2000;290:1368–1372.
  • Thind SK, Taborda CP, Nosanchuk JD. Dendritic cell interactions with histoplasma and Paracoccidioides. Virulence. 2015;6:424–432.
  • Kischkel B, Boniche-Alfaro C, de Godoy Menezes I, et al. Immunoproteomic and immunopeptidomic analyses of Histoplasma capsulatum reveal promiscuous and conserved epitopes among fungi with vaccine potential. Front Immunol. 2021;12:764501.
  • Gildea L, Morris R, Newman S. Histoplasma capsulatum yeasts are phagocytosed via very late antigen-5, killed, and processed for antigen presentation by human dendritic cells. J Immunol Baltim Md. 2001;166:1049–1056.
  • Gildea LA, Ciraolo GM, Morris RE, et al. Human dendritic cell activity against Histoplasma capsulatum is mediated via phagolysosomal fusion. Infect Immun. 2005;73:6803–6811.
  • Newman SL, Gootee L, Kidd C, et al. Activation of human macrophage fungistatic activity against Histoplasma capsulatum upon adherence to type 1 collagen matrices. J Immunol. 1997;158:1779–1786.
  • Chang T-H, Huang J-H, Lin H-C, et al. Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum. PLoS Pathog. 2017;13:e1006485.
  • Van Prooyen N, Henderson CA, Hocking Murray D, et al. CD103+ conventional dendritic cells are critical for TLR7/9-dependent host defense against Histoplasma capsulatum, an endemic fungal pathogen of humans. PLoS Pathog. 2016;12:e1005749.
  • Baughman RP, Kim CK, Vinegar A, et al. The pathogenesis of experimental pulmonary histoplasmosis. Correlative studies of histopathology, bronchoalveolar lavage, and respiratory function. Am Rev Respir Dis. 1986;134:771–776.
  • Newman SL, Gootee L, Gabay JE. Human neutrophil-mediated fungistasis against Histoplasma capsulatum. Localization of fungistatic activity to the azurophil granules. J Clin Invest. 1993;92:624–631.
  • Newman SL, Gootee L, Gabay JE, et al. Identification of constituents of human neutrophil azurophil granules that mediate fungistasis against histoplasma capsulatum. Infect Immun. 2000;68:5668–5672.
  • Thompson-Souza GA, Abed U, Goosmann C, et al. Histoplasma capsulatum-induced extracellular DNA trap release in human neutrophils. Cell Microbiol. 2020;22:e13195.
  • Fuchs TA, Abed U, Goosmann C, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176:231–241.
  • Papayannopoulos V, Metzler KD, Hakkim A, et al. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol. 2010;191:677–691.
  • Tewari RP, Von Behren LA. Immune responses in histoplasmosis, a prototype of respiratory mycoses. Indian J Chest Dis Allied Sci. 2000;42:265–269.
  • Zhou P, Freidag BL, Caldwell CC, et al. Perforin is required for primary immunity to Histoplasma capsulatum. J Immunol Baltim Md. 2001;166:1968–1974.
  • Cohen NR, Tatituri RV, Rivera A, et al. Innate recognition of cell wall β-glucans drives invariant natural killer T cell responses against fungi. Cell Host Microbe. 2011;10:437–450.
  • Woods JP. Revisiting old friends: developments in understanding = Histoplasma capsulatum pathogenesis. J Microbiol Seoul Korea. 2016;54:265–276.
  • Heninger E, Hogan LH, Karman J, et al. Characterization of the = Histoplasma capsulatum-induced granuloma. J Immunol Baltim Md. 2006;177:3303–3313.
  • Mukhopadhyay S, Farver CF, Vaszar LT, et al. Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries. J Clin Pathol. 2012;65:51–57.
  • Mukhopadhyay S, Wilcox BE, Myers JL, et al. Pulmonary necrotizing granulomas of unknown cause: clinical and pathologic analysis of 131 patients with completely resected nodules. Chest. 2013;144:813–824.
  • Allen HL, Deepe GS. B cells and CD4-CD8- T cells are key regulators of the severity of reactivation histoplasmosis. J Immunol Baltim Md. 2006;177:1763–1771.
  • Clemons KV, Darbonne WC, Curnutte JT, et al. Experimental histoplasmosis in mice treated with anti-murine interferon-gamma antibody and in interferon-gamma gene knockout mice. Microbes Infect. 2000;2:997–1001.
  • Shen Q, Rappleye CA. Living within the macrophage: dimorphic fungal pathogen intracellular metabolism. Front Cell Infect Microbiol. 2020;10:592259.
  • Shen Q, Ray SC, Evans HM, et al. Metabolism of gluconeogenic substrates by an intracellular fungal pathogen circumvents nutritional limitations within macrophages. MBio. 2020;11:e02712–19.
  • Garfoot AL, Zemska O, Rappleye CA. Histoplasma capsulatum depends on de novo vitamin biosynthesis for intraphagosomal proliferation. Infect Immun. 2014;82:393–404.
  • Brechting PJ, Rappleye CA. Histoplasma responses to nutritional immunity imposed by macrophage activation. J Fungi. 2019;5:45.
  • Hilty J, George Smulian A, Newman SL. Histoplasma capsulatum utilizes siderophores for intracellular iron acquisition in macrophages. Med Mycol. 2011;49:633–642.
  • Hwang LH, Mayfield JA, Rine J, et al. Histoplasma requires SID1, a member of an iron-regulated siderophore gene cluster, for host colonization. PLoS Pathog. 2008;4:e1000044.
  • Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe. 2013;13:509–519.
  • Finkelstein RA, Sciortino CV, McIntosh MA. Role of Iron in microbe-host interactions. Rev infect dis. 1983;5:S759–777.
  • Howard DH. Iron gathering by zoopathogenic fungi. FEMS Immunol Med Microbiol. 2004;40:95–100.
  • Newman SL, Gootee L, Brunner G, et al. Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis. J Clin Invest. 1994;93:1422–1429.
  • Subramanian Vignesh K, Landero Figueroa JA, Porollo A, et al. Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival. Immunity. 2013;39:697–710.
  • Dade J, DuBois JC, Pasula R, et al. HcZrt2, a zinc responsive gene, is indispensable for the survival of Histoplasma capsulatum in vivo. Med Mycol. 2016;54:865–875.
  • Rossi DC, Figueroa JAL, Buesing WR, et al. A metabolic inhibitor arms macrophages to kill intracellular fungal pathogens by manipulating zinc homeostasis. J Clin Invest. 2021;131:147268.
  • Albuquerque PC, Nakayasu ES, Rodrigues ML, et al. Vesicular transport in Histoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes. Cell Microbiol. 2008;10:1695–1710.
  • Rodrigues ML, Nakayasu ES, Oliveira DL, et al. Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence. Eukaryot Cell. 2008;7:58–67.
  • Vallejo MC, Matsuo AL, Ganiko L, et al. The pathogenic fungus paracoccidioides brasiliensis exports extracellular vesicles containing highly immunogenic α-galactosyl epitopes. Eukaryot Cell. 2011;10:343–351.
  • Vargas G, Rocha JD, Oliveira DL, et al. Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans. Cell Microbiol. 2015;17:389–407.
  • Rayner S, Bruhn S, Vallhov H, et al. Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis. Sci Rep. 2017;7:39742.
  • Johansson HJ, Vallhov H, Holm T, et al. Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin. Sci Rep. 2018;8:9182.
  • Zamith-Miranda D, Nimrichter L, Rodrigues ML, et al. Fungal extracellular vesicles: modulating host-pathogen interactions by both the fungus and the host. Microbes Infect. 2018;20:501–504.
  • Piffer AC, Kuczera D, Rodrigues ML, et al. The paradoxical and still obscure properties of fungal extracellular vesicles. Mol Immunol. 2021;135:137–146.
  • Reis FCG, Costa JH, Honorato L, et al. Small molecule analysis of extracellular vesicles produced by cryptococcus gattii: identification of a tripeptide controlling cryptococcal infection in an invertebrate host model. Front Immunol. 2021;12:654574.
  • Vargas G, Honorato L, Guimarães AJ, et al. Protective effect of fungal extracellular vesicles against murine candidiasis. Cell Microbiol. 2020;22:e13238.
  • Zamith-Miranda D, Alves LR, Nakayasu ES, et al. Lessons learned from studying Histoplasma capsulatum extracellular vesicles. Curr Top Microbiol Immunol. 2021;432:13–18.
  • Honorato L, de Araujo JFD, Ellis CC, et al. Extracellular vesicles regulate biofilm formation and yeast-to-hypha differentiation in candida albicans. MBio. 2022;0030122. DOI:10.1128/mbio.00301-22.
  • Baltazar LM, Nakayasu ES, Sobreira TJ, et al. Antibody binding alters the characteristics and contents of extracellular vesicles released by Histoplasma capsulatum. mSphere. 2016;1:e00085–15.
  • Baltazar LM, Zamith-Miranda D, Burnet MC, et al. Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages. Sci Rep. 2018;8:8065.
  • Cleare LG, Zamith D, Heyman HM, et al. Media matters! alterations in the loading and release of Histoplasma capsulatum extracellular vesicles in response to different nutritional milieus. Cell Microbiol. 2020;22:e13217.