201
Views
16
CrossRef citations to date
0
Altmetric
Perspective

Crohn’s as an immune deficiency: from apparent paradox to evolving paradigm

&
Pages 17-30 | Published online: 10 Jan 2014

References

  • Sancho-Shimizu V, Perez de Diego R, Jouanguy E, Zhang SY, Casanova JL. Inborn errors of anti-viral interferon immunity in humans. Curr. Opin. Virol. 1(6), 487–496 (2011).
  • Casanova JL, Abel L. Primary immunodeficiencies: a field in its infancy. Science 317(5838), 617–619 (2007).
  • Tyler KL. Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret’s. Herpes 11(Suppl. 2), 57A–64A (2004).
  • Hartwig NG, Warris A, van de Vosse E et al. ‘Mycobacterium tilburgii’ infection in two immunocompromised children: importance of molecular tools in culture-negative mycobacterial disease diagnosis. J. Clin. Microbiol. 49(12), 4409–4411 (2011).
  • Casanova JL, Abel L, Quintana-Murci L. Human TLRs and IL-1Rs in host defense: natural insights from evolutionary, epidemiological, and clinical genetics. Annu. Rev. Immunol. 29, 447–491 (2011).
  • Picard C, Casanova JL, Puel A. Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IkBa deficiency. Clin. Microbiol. Rev. 24(3), 490–497 (2011).
  • Aksentijevich I, Kastner DL. Genetics of monogenic autoinflammatory diseases: past successes, future challenges. Nat. Rev. Rheumatol. 7(8), 469–478 (2011).
  • Bussone G, Mouthon L. Autoimmune manifestations in primary immune deficiencies. Autoimmun. Rev. 8(4), 332–336 (2009).
  • Arason GJ, Jorgensen GH, Ludviksson BR. Primary immunodeficiency and autoimmunity: lessons from human diseases. Scand. J. Immunol. 71(5), 317–328 (2010).
  • Zhang Q, Davis JC, Dove CG, Su HC. Genetic, clinical, and laboratory markers for DOCK8 immunodeficiency syndrome. Dis. Markers 29(3–4), 131–139 (2010).
  • Ombrello MJ, Remmers EF, Sun G et al. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N. Engl. J. Med. 366(4), 330–338 (2012).
  • Vinh DC, Patel SY, Uzel G et al. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 115(8), 1519–1529 (2010).
  • Hsu AP, Sampaio EP, Khan J et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 118(10), 2653–2655 (2011).
  • Ostergaard P, Simpson MA, Connell FC et al. Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat. Genet. 43(10), 929–931 (2011).
  • Calado RT. Telomeres and marrow failure. Hematology Am. Soc. Hematol. Educ. Program 338–343 (2009).
  • Singh S, Blanchard A, Walker JR, Graff LA, Miller N, Bernstein CN. Common symptoms and stressors among individuals with inflammatory bowel diseases. Clin. Gastroenterol. Hepatol. 9(9), 769–775 (2011).
  • Burbige EJ, Huang SH, Bayless TM. Clinical manifestations of Crohn’s disease in children and adolescents. Pediatrics 55(6), 866–871 (1975).
  • Reinisch W, Wang Y, Oddens BJ, Link R. C-reactive protein, an indicator for maintained response or remission to infliximab in patients with Crohn’s disease: a post-hoc analysis from ACCENT I. Aliment. Pharmacol. Ther. 35(5), 568–576 (2012).
  • Goldbach-Mansky R. Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1. Clin. Exp. Immunol. 167(3), 391–404 (2012).
  • Ozkurede VU, Franchi L. Immunology in clinic review series; focus on autoinflammatory diseases: role of inflammasomes in autoinflammatory syndromes. Clin. Exp. Immunol. 167(3), 382–390 (2012).
  • Glocker EO, Kotlarz D, Boztug K et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N. Engl. J. Med. 361(21), 2033–2045 (2009).
  • Marrakchi S, Guigue P, Renshaw BR et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N. Engl. J. Med. 365(7), 620–628 (2011).
  • Siddiqui S, Anderson VL, Hilligoss DM et al. Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin. Infect. Dis. 45(6), 673–681 (2007).
  • Freeman AF, Marciano BE, Anderson VL, Uzel G, Costas C, Holland SM. Corticosteroids in the treatment of severe nocardia pneumonia in chronic granulomatous disease. Pediatr. Infect. Dis. J. 30(9), 806–808 (2011).
  • Leiding JW, Freeman AF, Marciano BE et al. Corticosteroid therapy for liver abscess in chronic granulomatous disease. Clin. Infect. Dis. 54(5), 694–700 (2012).
  • Sebire NJ, Haselden S, Malone M, Davies EG, Ramsay AD. Isolated EBV lymphoproliferative disease in a child with Wiskott–Aldrich syndrome manifesting as cutaneous lymphomatoid granulomatosis and responsive to anti-CD20 immunotherapy. J. Clin. Pathol. 56(7), 555–557 (2003).
  • Milone MC, Tsai DE, Hodinka RL et al. Treatment of primary Epstein–Barr virus infection in patients with x-linked lymphoproliferative disease using B-cell-directed therapy. Blood 105(3), 994–996 (2005).
  • Henter JI, Horne A, Aricó M et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr. Blood Cancer 48(2), 124–131 (2007).
  • Carmona EM, Limper AH. Update on the diagnosis and treatment of Pneumocystis pneumonia. Ther. Adv. Respir. Dis. 5(1), 41–59 (2011).
  • Marciano BE, Rosenzweig SD, Kleiner DE et al. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics 114(2), 462–468 (2004).
  • Schäppi MG, Smith VV, Goldblatt D, Lindley KJ, Milla PJ. Colitis in chronic granulomatous disease. Arch. Dis. Child. 84(2), 147–151 (2001).
  • Marks DJ, Miyagi K, Rahman FZ, Novelli M, Bloom SL, Segal AW. Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn’s disease. Am. J. Gastroenterol. 104(1), 117–124 (2009).
  • Roe T, Schonfeld N, Thomas D, Gilsanz V, Atkinson J, Issacs H. Regional enteritis and glycogen storage disease type IB. Lancet 1(8385), 1077 (1984).
  • Yamaguchi T, Ihara K, Matsumoto T et al. Inflammatory bowel disease-like colitis in glycogen storage disease type 1b. Inflamm. Bowel Dis. 7(2), 128–132 (2001).
  • Agarwal S, Smereka P, Harpaz N, Cunningham-Rundles C, Mayer L. Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal disease. Inflamm. Bowel Dis. 17(1), 251–259 (2011).
  • Daniels JA, Lederman HM, Maitra A, Montgomery EA. Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. Am. J. Surg. Pathol. 31(12), 1800–1812 (2007).
  • Ishii E, Matui T, Iida M, Inamitu T, Ueda K. Chediak-Higashi syndrome with intestinal complication. Report of a case. J. Clin. Gastroenterol. 9(5), 556–558 (1987).
  • Rohr J, Pannicke U, Döring M et al. Chronic inflammatory bowel disease as key manifestation of atypical ARTEMIS deficiency. J. Clin. Immunol. 30(2), 314–320 (2010).
  • Cohen MS, Isturiz RE, Malech HL et al. Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi. Am. J. Med. 71(1), 59–66 (1981).
  • Winkelstein JA, Marino MC, Johnston RB Jr et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 79(3), 155–169 (2000).
  • Ambruso DR, McCabe ER, Anderson D et al. Infectious and bleeding complications in patients with glycogenosis Ib. Am. J. Dis. Child. 139(7), 691–697 (1985).
  • Visser G, Rake JP, Fernandes J et al. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type IB: results of the European Study on Glycogen Storage Disease type I. J. Pediatr. 137(2), 187–191 (2000).
  • Dieckgraefe BK, Korzenik JR, Husain A, Dieruf L. Association of glycogen storage disease 1b and Crohn disease: results of a North American survey. Eur. J. Pediatr. 161(Suppl. 1), S88–S92 (2002).
  • Yamaguchi T, Ihara K, Matsumoto T et al. Inflammatory bowel disease-like colitis in glycogen storage disease type 1b. Inflamm. Bowel Dis. 7(2), 128–132 (2001).
  • Sloan JM, Cameron CH, Maxwell RJ, McCluskey DR, Collins JS. Colitis complicating chronic granulomatous disease: a clinicopathological case report. Gut 38(4), 619–622 (1996).
  • Liu S, Russo PA, Baldassano RN, Sullivan KE. CD68 expression is markedly different in Crohn’s disease and the colitis associated with chronic granulomatous disease. Inflamm. Bowel Dis. 15(8), 1213–1217 (2009).
  • Davis MK, Rufo PA, Polyak SF, Weinstein DA. Adalimumab for the treatment of Crohn-like colitis and enteritis in glycogen storage disease type IB. J. Inherit. Metab. Dis. (2008).
  • Wang J, Mayer L, Cunningham-Rundles C. Use of GM-CSF in the treatment of colitis associated with chronic granulomatous disease. J. Allergy Clin. Immunol. 115(5), 1092–1094 (2005).
  • Uzel G, Orange JS, Poliak N, Marciano BE, Heller T, Holland SM. Complications of tumor necrosis factor-a blockade in chronic granulomatous disease-related colitis. Clin. Infect. Dis. 51(12), 1429–1434 (2010).
  • Freudenberg F, Wintergerst U, Roesen-Wolff A et al. Therapeutic strategy in p47-phox deficient chronic granulomatous disease presenting as inflammatory bowel disease. J. Allergy Clin. Immunol. 125(4), 943–946.e1 (2010).
  • Roe TF, Coates TD, Thomas DW, Miller JH, Gilsanz V. Brief report: treatment of chronic inflammatory bowel disease in glycogen storage disease type IB with colony-stimulating factors. N. Engl. J. Med. 326(25), 1666–1669 (1992).
  • Visser G, Rake JP, Labrune P et al. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1. Eur. J. Pediatr. 161(Suppl. 1), S83–S87 (2002).
  • Visser G, Rake JP, Labrune P et al.; European Study on Glycogen Storage Disease Type I. Consensus guidelines for management of glycogen storage disease type 1b – European Study on Glycogen Storage Disease Type 1. Eur. J. Pediatr. 161(Suppl. 1), S120–S123 (2002).
  • Myrup B, Valerius NH, Mortensen PB. Treatment of enteritis in chronic granulomatous disease with granulocyte colony stimulating factor. Gut 42(1), 127–130 (1998).
  • Kasahara Y, Iwai K, Yachie A et al. Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1)-mediated apoptosis of neutrophils. Blood 89(5), 1748–1753 (1997).
  • Sanmun D, Witasp E, Jitkaew S et al. Involvement of a functional NADPH oxidase in neutrophils and macrophages during programmed cell clearance: implications for chronic granulomatous disease. Am. J. Physiol., Cell Physiol. 297(3), C621–C631 (2009).
  • Brown JR, Goldblatt D, Buddle J, Morton L, Thrasher AJ. Diminished production of anti-inflammatory mediators during neutrophil apoptosis and macrophage phagocytosis in chronic granulomatous disease (CGD). J. Leukoc. Biol. 73(5), 591–599 (2003).
  • Segal BH, Han W, Bushey JJ et al. NADPH oxidase limits innate immune responses in the lungs in mice. PLoS One 5(3), e9631 (2010).
  • Brown KL, Bylund J, MacDonald KL et al. ROS-deficient monocytes have aberrant gene expression that correlates with inflammatory disorders of chronic granulomatous disease. Clin. Immunol. 129(1), 90–102 (2008).
  • Morgenstern DE, Gifford MA, Li LL, Doerschuk CM, Dinauer MC. Absence of respiratory burst in x-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J. Exp. Med. 185(2), 207–218 (1997).
  • Schäppi M, Deffert C, Fiette L et al. Branched fungal b-glucan causes hyperinflammation and necrosis in phagocyte NADPH oxidase-deficient mice. J. Pathol. 214(4), 434–444 (2008).
  • Petersen JE, Hiran TS, Goebel WS et al. Enhanced cutaneous inflammatory reactions to Aspergillus fumigatus in a murine model of chronic granulomatous disease. J. Invest. Dermatol. 118(3), 424–429 (2002).
  • Leuzzi R, Bánhegyi G, Kardon T et al. Inhibition of microsomal glucose-6-phosphate transport in human neutrophils results in apoptosis: a potential explanation for neutrophil dysfunction in glycogen storage disease type 1b. Blood 101(6), 2381–2387 (2003).
  • Visser G, de Jager W, Verhagen LP et al. Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients. J. Inherit. Metab. Dis. 35(2), 287–300 (2012).
  • Zholudev A, Zurakowski D, Young W, Leichtner A, Bousvaros A. Serologic testing with ANCA, ASCA, and anti-OmpC in children and young adults with Crohn’s disease and ulcerative colitis: diagnostic value and correlation with disease phenotype. Am. J. Gastroenterol. 99(11), 2235–2241 (2004).
  • Yu JE, De Ravin SS, Uzel G et al. High levels of Crohn’s disease-associated anti-microbial antibodies are present and independent of colitis in chronic granulomatous disease. Clin. Immunol. 138(1), 14–22 (2011).
  • Davis MK, Valentine JF, Weinstein DA, Polyak S. Antibodies to CBir1 are associated with glycogen storage disease type IB. J. Pediatr. Gastroenterol. Nutr. 51(1), 14–18 (2010).
  • Marks DJ, Harbord MW, MacAllister R et al. Defective acute inflammation in Crohn’s disease: a clinical investigation. Lancet 367(9511), 668–678 (2006).
  • Harbord MW, Marks DJ, Forbes A, Bloom SL, Day RM, Segal AW. Impaired neutrophil chemotaxis in Crohn’s disease relates to reduced production of chemokines and can be augmented by granulocyte-colony stimulating factor. Aliment. Pharmacol. Ther. 24(4), 651–660 (2006).
  • Segal AW, Loewi G. Neutrophil dysfunction in Crohn’s disease. Lancet 2(7979), 219–221 (1976).
  • Wandall JH, Binder V. Leucocyte function in Crohn’s disease: studies on mobilisation using a quantitative skin window technique and on the function of circulating polymorphonuclear leucocytes in vitro. Gut 23(3), 173–180 (1982).
  • Belsheim J, Gnarpe H, Persson S. Granulocyte chemotaxis in Crohn’s disease. Acta Chir. Scand. 147(3), 197–200 (1981).
  • Curran FT, Keighley MR. Neutrophil motility in Crohn’s disease. Digestion 48(2), 104–112 (1991).
  • Hayee B, Rahman FZ, Tempero J et al. The neutrophil respiratory burst and bacterial digestion in Crohn’s disease. Dig. Dis. Sci. 56(5), 1482–1488 (2011).
  • Kuhns DB, Alvord WG, Heller T et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N. Engl. J. Med. 363(27), 2600–2610 (2010).
  • Smith AM, Rahman FZ, Hayee B et al. Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn’s disease. J. Exp. Med. 206(9), 1883–1897 (2009).
  • Sewell GW, Rahman FZ, Levine AP et al. Defective tumor necrosis factor release from Crohn’s disease macrophages in response to toll-like receptor activation: relationship to phenotype and genome-wide association susceptibility loci. Inflamm. Bowel Dis. 18(11), 2120–2127 (2012).
  • Goldstein JI, Kominsky DJ, Jacobson N et al. Defective leukocyte GM-CSF receptor (CD116) expression and function in inflammatory bowel disease. Gastroenterology 141(1), 208–216 (2011).
  • Luisetti M, Kadija Z, Mariani F, Rodi G, Campo I, Trapnell BC. Therapy options in pulmonary alveolar proteinosis. Ther. Adv. Respir. Dis. 4(4), 239–248 (2010).
  • Hambleton S, Salem S, Bustamante J et al. IRF8 mutations and human dendritic-cell immunodeficiency. N. Engl. J. Med. 365(2), 127–138 (2011).
  • Bigley V, Haniffa M, Doulatov S et al. The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J. Exp. Med. 208(2), 227–234 (2011).
  • Al-Muhsen S, Casanova JL. The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J. Allergy Clin. Immunol. 122(6), 1043–51; quiz 1052 (2008).
  • Bustamante J, Picard C, Boisson-Dupuis S, Abel L, Casanova JL. Genetic lessons learned from X-linked Mendelian susceptibility to mycobacterial diseases. Ann. NY Acad. Sci. 1246, 92–101 (2011).
  • de Saint Basile G, Ménasché G, Latour S. Inherited defects causing hemophagocytic lymphohistiocytic syndrome. Ann. NY Acad. Sci. 1246, 64–76 (2011).
  • Stark Z, Savarirayan R. Osteopetrosis. Orphanet J. Rare Dis. 4, 5 (2009).
  • Rademakers R, Baker M, Nicholson AM et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat. Genet. 44(2), 200–205 (2012).
  • Suzuki T, Maranda B, Sakagami T et al. Hereditary pulmonary alveolar proteinosis caused by recessive CSF2RB mutations. Eur. Respir. J. 37(1), 201–204 (2011).
  • Ogura Y, Bonen DK, Inohara N et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411(6837), 603–606 (2001).
  • Hugot JP, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411(6837), 599–603 (2001).
  • MacMicking JD, Taylor GA, McKinney JD. Immune control of tuberculosis by IFN-g-inducible LRG-47. Science 302(5645), 654–659 (2003).
  • Singh SB, Davis AS, Taylor GA, Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313(5792), 1438–1441 (2006).
  • Parkes M, Barrett JC, Prescott NJ et al.; Wellcome Trust Case Control Consortium. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat. Genet. 39(7), 830–832 (2007).
  • Travassos LH, Carneiro LA, Ramjeet M et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11(1), 55–62 (2010).
  • Cooney R, Baker J, Brain O et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16(1), 90–97 (2010).
  • Freudenberg F, Wintergerst U, Roesen-Wolff A et al. Therapeutic strategy in p47-phox deficient chronic granulomatous disease presenting as inflammatory bowel disease. J. Allergy Clin. Immunol. 125(4), 943–946.e1 (2010).
  • Muise AM, Snapper SB, Kugathasan S. The age of gene discovery in very early onset inflammatory bowel disease. Gastroenterology 143(2), 285–288 (2012).
  • Muise AM, Xu W, Guo CH et al.; NEOPICS. NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2. Gut 61(7), 1028–1035 (2012).
  • Bustamante J, Arias AA, Vogt G et al. Germline CYBB mutations that selectively affect macrophages in kindreds with x-linked predisposition to tuberculous mycobacterial disease. Nat. Immunol. 12(3), 213–221 (2011).
  • Hugot JP, Zaccaria I, Cavanaugh J et al.; for the IBD International Genetics Consortium. Prevalence of CARD15/NOD2 mutations in Caucasian healthy people. Am. J. Gastroenterol. 102(6), 1259–1267 (2007).
  • Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature 469(7330), 323–335 (2011).
  • Deretic V. Autophagy as an innate immunity paradigm: expanding the scope and repertoire of pattern recognition receptors. Curr. Opin. Immunol. 24(1), 21–31 (2012).
  • Inohara N, Ogura Y, Fontalba A et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J. Biol. Chem. 278(8), 5509–5512 (2003).
  • Girardin SE, Boneca IG, Viala J et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J. Biol. Chem. 278(11), 8869–8872 (2003).
  • Lala S, Ogura Y, Osborne C et al. Crohn’s disease and the NOD2 gene: a role for paneth cells. Gastroenterology 125(1), 47–57 (2003).
  • Richmond AL, Kabi A, Homer CR et al. The nucleotide synthesis enzyme CAD inhibits NOD2 antibacterial function in human intestinal epithelial cells. Gastroenterology 142(7), 1483–1492.e6 (2012).
  • Penack O, Smith OM, Cunningham-Bussel A et al. NOD2 regulates hematopoietic cell function during graft-versus-host disease. J. Exp. Med. 206(10), 2101–2110 (2009).
  • Wehkamp J, Harder J, Weichenthal M et al. NOD2 (CARD15) mutations in Crohn’s disease are associated with diminished mucosal a-defensin expression. Gut 53(11), 1658–1664 (2004).
  • Wehkamp J, Salzman NH, Porter E et al. Reduced Paneth cell α-defensins in ileal Crohn’s disease. Proc. Natl Acad. Sci. USA 102(50), 18129–18134 (2005).
  • Wehkamp J, Stange EF. A new look at Crohn’s disease: breakdown of the mucosal antibacterial defense. Ann. NY Acad. Sci. 1072, 321–331 (2006).
  • Wehkamp J, Stange EF. Paneth’s disease. J. Crohns Colitis 4(5), 523–531 (2010).
  • Herskovits AA, Auerbuch V, Portnoy DA. Bacterial ligands generated in a phagosome are targets of the cytosolic innate immune system. PLoS Pathog. 3(3), e51 (2007).
  • Coulombe F, Divangahi M, Veyrier F et al. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J. Exp. Med. 206(8), 1709–1716 (2009).
  • Pandey AK, Yang Y, Jiang Z et al. NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS Pathog. 5(7), e1000500 (2009).
  • Balamayooran T, Batra S, Balamayooran G et al. Receptor-interacting protein 2 controls pulmonary host defense to Escherichia coli infection via the regulation of interleukin-17A. Infect. Immun. 79(11), 4588–4599 (2011).
  • Hruz P, Zinkernagel AS, Jenikova G et al. NOD2 contributes to cutaneous defense against Staphylococcus aureus through α-toxin-dependent innate immune activation. Proc. Natl Acad. Sci. USA 106(31), 12873–12878 (2009).
  • Hsu LC, Ali SR, McGillivray S et al. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1β secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc. Natl Acad. Sci. USA 105(22), 7803–7808 (2008).
  • Kobayashi KS, Chamaillard M, Ogura Y et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307(5710), 731–734 (2005).
  • Gandotra S, Jang S, Murray PJ, Salgame P, Ehrt S. Nucleotide-binding oligomerization domain protein 2-deficient mice control infection with Mycobacterium tuberculosis. Infect. Immun. 75(11), 5127–5134 (2007).
  • Divangahi M, Mostowy S, Coulombe F et al. NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity. J. Immunol. 181(10), 7157–7165 (2008).
  • Coulombe F, Fiola S, Akira S, Cormier Y, Gosselin J. Muramyl dipeptide induces NOD2-dependent Ly6C(high) monocyte recruitment to the lungs and protects against influenza virus infection. PLoS One 7(5), e36734 (2012).
  • Zhang FR, Huang W, Chen SM et al. Genomewide association study of leprosy. N. Engl. J. Med. 361(27), 2609–2618 (2009).
  • Berrington WR, Macdonald M, Khadge S et al. Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states. J. Infect. Dis. 201(9), 1422–1435 (2010).
  • Austin CM, Ma X, Graviss EA. Common nonsynonymous polymorphisms in the NOD2 gene are associated with resistance or susceptibility to tuberculosis disease in African Americans. J. Infect. Dis. 197(12), 1713–1716 (2008).
  • Pan H, Dai Y, Tang S, Wang J. Polymorphisms of NOD2 and the risk of tuberculosis: a validation study in the Chinese population. Int. J. Immunogenet. 39(3), 233–240 (2012).
  • Ferwerda G, Girardin SE, Kullberg BJ et al. NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog. 1(3), 279–285 (2005).
  • Brooks MN, Rajaram MV, Azad AK et al. NOD2 controls the nature of the inflammatory response and subsequent fate of Mycobacterium tuberculosis and M. bovis BCG in human macrophages. Cell. Microbiol. 13(3), 402–418 (2011).
  • Juárez E, Carranza C, Hernández-Sánchez F et al. NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans. Eur. J. Immunol. 42(4), 880–889 (2012).
  • Slater M, Parsonnet J, Banaei N. Investigation of false-positive results given by the QuantiFERON-TB Gold In-Tube assay. J. Clin. Microbiol. 50(9), 3105–3107 (2012).
  • Browne SK, Burbelo PD, Chetchotisakd P et al. Adult-onset immunodeficiency in Thailand and Taiwan. N. Engl. J. Med. 367(8), 725–734 (2012).
  • Colombel JF, Grandbastien B, Gower-Rousseau C et al. Clinical characteristics of Crohn’s disease in 72 families. Gastroenterology 111(3), 604–607 (1996).
  • Franke A, McGovern DP, Barrett JC et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat. Genet. 42(12), 1118–1125 (2010).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.