Enhanced protection to Mycobacterium tuberculosis infection in IL-10-deficient mice is accompanied by early and enhanced Th1 responses in the lung.
IL-10 regulates the balance of an immune response between pathogen clearance and immunopathology. We show here that Mycobacterium tuberculosis (Mtb) infection in the absence of IL-10 (IL-10(-/-) mice) results in reduced bacterial loads in the lung. This reduction was preceded by an accelerated and enhanced IFN-γ response in the lung, an increased influx of CD4(+) T cells into the lung, and enhanced production of chemokines and cytokines, including CXCL10 and IL-17, in both the lung and the serum. Neutralization of IL-17 affected neither the enhanced production of CXCL10 nor the accumulation of IFN-γ-producing T cells in the lungs, but led to reduced numbers of granulocytes in the lung and reduced bacterial loads in the spleens of Mtb-infected mice. This suggests that IL-17 may contribute to dissemination of Mtb.
Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
Paul S
PS
Redford
Andre
A
Boonstra
Simon
S
Read
Jonathan
J
Pitt
Christine
C
Graham
Evangelos
E
Stavropoulos
Gregory J
GJ
Bancroft
Anne
A
O'Garra
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D058491:Bacterial Load / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D058408:Th1-Th2 Balance / Q000187:drug effects; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*
D019138:Antibodies, Blocking; D054357:Chemokine CXCL10; D020381:Interleukin-17; D016753:Interleukin-10; D007371:Interferon-gamma