CD4+ cells play a limited role in murine lung infection with Mycobacterium kansasii.
Mycobacterium kansasii has emerged as an important nontuberculous mycobacterium that can cause severe infection in the immunocompromised host, especially in human immunodeficiency virus-infected patients. However, little is known about the pathogenesis of this infection. Because patients suffering from M. kansasii infection are severely compromised in their cellular immune response, we studied the course of infection in CD4+ cell knockout (KO) mice. Wild-type (WT) mice and CD4+ KO mice were infected with 10(5) cfu of M. kansasii. Although previously shown to be susceptible to Mycobacterium tuberculosis infection, CD4+ KO mice demonstrated no impairment in clearing infection with M. kansasii when compared with WT animals, despite reduced pulmonary inflammation (reduced granuloma formation and lymphocyte infiltration in the lungs). Pulmonary IFN-gamma levels and M. kansasii-induced IFN-gamma production by splenocytes from infected animals were reduced in CD4+ KO mice, confirming that these mice were defective in the M. kansasii-specific T helper cell type 1 immune response. Furthermore, mice deficient for IFN-gamma, IL-12p35, IL-12p40, or IL-18 also displayed a normal host defense against pulmonary infection with M. kansasii. These data suggest that CD4+ cells, IFN-gamma, and an intact T helper cell type 1 response play a limited role in protective immunity against pulmonary M. kansasii infection.
Wieland
Catharina W
CW
Laboratory of Experimental Internal Medicine, G2-132, Academic Medical Center, University of Amsterdam, The Netherlands. c.wieland@amc.uva.nl
Florquin
Sandrine
S
Pater
Jennie M
JM
Weijer
Sebastiaan
S
van der Poll
Tom
T
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18 / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology*; D019909:Mycobacterium kansasii / Q000472:pathogenicity; D011014:Pneumonia / Q000276:immunology; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology
D015704:CD4 Antigens; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D021122:Protein Subunits; D018664:Interleukin-12; D007371:Interferon-gamma