IL-22 Protects against Tissue Damage during Cutaneous Leishmaniasis.
Cutaneous leishmaniasis is a disease characterized by ulcerating skin lesions, the resolution of which requires an effective, but regulated, immune response that limits parasite growth without causing permanent tissue damage. While mechanisms that control the parasites have been well studied, the factors regulating immunopathologic responses are less well understood. IL-22, a member of the IL-10 family of cytokines, can contribute to wound healing, but in other instances promotes pathology. Here we investigated the role of IL-22 during leishmania infection, and found that IL-22 limits leishmania-induced pathology when a certain threshold of damage is induced by a high dose of parasites. Il22-/- mice developed more severe disease than wild-type mice, with significantly more pathology at the site of infection, and in some cases permanent loss of tissue. The increased inflammation was not due to an increased parasite burden, but rather was associated with the loss of a wound healing phenotype in keratinocytes. Taken together, these studies demonstrate that during cutaneous leishmaniasis, IL-22 can play a previously unappreciated role in controlling leishmania-induced immunopathology.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States of America.
Ciara
C
Gimblet
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States of America.
Michael A
MA
Loesche
Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciências e Tecnologia-Doenças Tropicais, Salvador, Bahia, Brazil; Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Lucas
L
Carvalho
Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciências e Tecnologia-Doenças Tropicais, Salvador, Bahia, Brazil; Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Edgar M
EM
Carvalho
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States of America.
Elizabeth A
EA
Grice
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States of America.
David
D
Artis
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States of America.
Phillip
P
Scott
D000818:Animals; D005260:Female; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000503:physiopathology; D014945:Wound Healing; D000097043:Interleukin-22
D007378:Interleukins; D000097043:Interleukin-22