Lack of IL-10 alters inflammatory and immune responses during pulmonary Mycobacterium tuberculosis infection.
Failure of mice to produce IL-10 has no effect on the bacterial burden of Mycobacterium tuberculosis infection in the lungs over the first 4-5 months of the disease. We show here that after 185 days of the infection, IL-10 gene disrupted (IL-10 KO) mice showed evidence of bacterial regrowth, began to show signs of wasting, and were moribund. We assessed the status of the acquired immune response and compared the lung lymphocyte cell populations, as well as the expression of Th1 (IL-12 and IFNgamma) and immunosuppressive (TGFbeta) cytokines, between IL-10 KO and wild type mice. The results demonstrated that at 60 days of the infection in the absence of IL-10 there was an increased expression of Th1 type immunity and an overall lack of control of the inflammatory responses. After 185 days of the infection, in the absence of IL-10 there was excessive pulmonary inflammation and increased expression of inflammatory cytokine TNFalpha. These results imply therefore that IL-10 plays a central role in dampening of the Th1 response and protection against chronic lung inflammation in the M. tuberculosis infected lung, and the complete removal of this regulatory component eventually leads to disease progression.
Higgins
David M
DM
Department of Microbiology, Mycobacteria Research Laboratories, Colorado State University, Fort Collins, CO 80523, USA.
Sanchez-Campillo
Joaquin
J
Rosas-Taraco
Adrian G
AG
Lee
Eric J
EJ
Orme
Ian M
IM
Gonzalez-Juarrero
Mercedes
M
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000172:deficiency* / Q000276:immunology; D008168:Lung / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000302:isolation & purification; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10