Interleukin-10 production by lung macrophages in CBA xid mutant mice infected with Mycobacterium tuberculosis.
Mice on the CBA inbred strain background expressing the well characterized mutation designated xid in the cytoplasmic signalling enzyme Bruton's protein kinase have been previously noted to illustrate shifts in T helper type 1 (Th1)/Th2 immunity which is underlined by an apparent failure to produce the regulatory cytokine interleukin-10. In the current study we examined if this extended to infection with Mycobacterium tuberculosis, which also depends on Th1 immunity. Contrary to expectations, xid mice showed evidence of a transient early susceptibility to pulmonary infection, changes in macrophage morphology, and decreased activation of lung natural killer cells, while showing evidence of substantial IL-10 production and accumulation in lung lesions macrophages, but paradoxically this did not influence the course of the chronic disease. In addition, macrophages from the lungs of xid mice also expressed high levels of CD14. These observations suggest that the xid mutation in cellular signalling has much wider effects on the immune system than previously thought.
Junqueira-Kipnis
Ana Paula
AP
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins 80523, USA.
Kipnis
Andre
A
Henao Tamayo
Marcela
M
Harton
Marisa
M
Gonzalez Juarrero
Mercedes
M
Basaraba
Randall J
RJ
Orme
Ian M
IM
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D016753:Interleukin-10 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008168:Lung / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology
D018950:Lipopolysaccharide Receptors; D016753:Interleukin-10; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse