Photodynamic therapy induces an immune response against a bacterial pathogen

Ying-Ying Huang Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Guangxi Medical University, Guangxi 530027, China; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Guangxi Medical University, Guangxi 530027, China

Masamitsu Tanaka Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan; Department of Integrated Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan; Department of Integrated Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan

Daniela Vecchio Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA

Maria Garcia-Diaz Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona 08017, Spain; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona 08017, Spain

Julie Chang Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Chemistry, Harvard University, Cambridge, MA 02138, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Chemistry, Harvard University, Cambridge, MA 02138, USA

Yuji Morimoto Department of Integrated Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan; Department of Integrated Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan

Michael R Hamblin Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. [email protected]; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. [email protected]

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Abstract

Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that both arms of the host immune system (innate and adaptive) are activated. When PDT is used for infectious disease, however, it has been assumed that the direct antimicrobial PDT effect dominates. Murine arthritis caused by methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT with intravenously injected Photofrin^®. PDT with intra-articular Photofrin produced a biphasic dose response that killed bacteria without destroying host neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria while preserving neutrophils. We used bioluminescence imaging to noninvasively monitor murine bacterial arthritis and found that PDT with intra-articular methylene blue was not only effective, but when used before infection, could protect the mice against a subsequent bacterial challenge. The data emphasize the importance of considering the host immune response in PDT for infectious disease.

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Financial & competing interests disclosure

Research in the Hamblin laboratory is supported by US NIH grant R01AI050875 M. Tanaka and Y Morimoto were supported by a Grant-in-Aid for Challenging Exploratory Research (23659628) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Photodynamic therapy induces an immune response against a bacterial pathogen

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Photodynamic therapy induces an immune response against a bacterial pathogen

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