Administration of IL-23 engages innate and adaptive immune mechanisms during fungal infection.
IL-23 is a key cytokine in promotion of chronic inflammation. Here, we address if its pro-inflammatory potential can be harnessed to protect against chronic cryptococcosis. Mice were infected with Cryptococcus neoformans and treated with recombinant IL-23. Administration of IL-23 led to prolonged survival and reduced fungal burden but was inferior to IL-12 treatment. Independent of endogenous IL-23/IL-12, IL-23 treatment induced an altered cytokine profile accompanied by marked changes in composition of the inflammatory infiltrate characterized by T cell and dendritic cell recruitment. Although IL-23 induced hallmarks of the T(h)17 pathway, also non-T cells produced IL-17A and IL-22. IL-23 treatment of T-cell-deficient mice resulted in increased IL-17A and IL-22 production and modulation of the cellular response at the site of infection with elevated expression of CD86 on macrophages. Our data show that IL-23 treatment induces innate and adaptive tissue inflammation with limited impact on resistance to chronic cryptococcosis.
Kleinschek
Melanie A
MA
Institute of Immunology, College of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany.
Müller
Uwe
U
Schütze
Nicole
N
Sabat
Robert
R
Straubinger
Reinhard K
RK
Blumenschein
Wendy M
WM
McClanahan
Terrill
T
Kastelein
Robert A
RA
Alber
Gottfried
G
D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D002478:Cells, Cultured; D003453:Cryptococcosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000472:pathogenicity*; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency / Q000235:genetics; D053759:Interleukin-23 / Q000008:administration & dosage*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000008:administration & dosage; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D013997:Time Factors
D000935:Antifungal Agents; D016207:Cytokines; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; C499308:Rag2 protein, mouse; D011994:Recombinant Proteins; C064658:RAG-1 protein; D018664:Interleukin-12