In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice.
The production of immunosuppressive cytokines, such as IL-10 and TGF-beta, has been documented in individuals diagnosed with active tuberculosis. In addition, IL-10 production is increased within the lungs of mice that have chronic mycobacterial infection. Therefore, we hypothesized that the down-regulatory properties of IL-10 might contribute to the reactivation of chronic Mycobacterium tuberculosis infection in mice. To determine the influence of IL-10 on the course of infection, transgenic mice producing increased amounts of IL-10 under the control of the IL-2 promotor were infected with M. tuberculosis via the respiratory route. Mice that overexpressed IL-10 showed no increase in susceptibility during the early stages of infection, but during the chronic phase of the infection showed evidence of reactivation tuberculosis with a highly significant increase in bacterial numbers within the lungs. Reactivation was associated with the formation of macrophage-dominated lesions, decreased mRNA production for TNF and IL-12p40, and a decrease in Ag-specific IFN-gamma secretion. These data support the hypothesis that IL-10 plays a pivotal role during the chronic/latent stage of pulmonary tuberculosis, with increased production playing a potentially central role in promoting reactivation tuberculosis.
Turner
Joanne
J
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins 80523, USA. joanne.turner@colostate.edu
Gonzalez-Juarrero
Mercedes
M
Ellis
Debi L
DL
Basaraba
Randy J
RJ
Kipnis
Andre
A
Orme
Ian M
IM
Cooper
Andrea M
AM
D000818:Animals; D040881:CD11a Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D015169:Colony Count, Microbial; D007108:Immune Tolerance; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D053762:Interleukin-12 Subunit p40; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D040881:CD11a Antigen; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma