Submitted to: Clinical Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/17/2002
Publication Date: 9/20/2002
Citation: SACCO, R.E., HAGEN, M., SANDOR, M., WEINSTOCK, J.V., LYNCH, R.G. ESTABLISHED TH1 GRANULOMATOUS RESPONSES INDUCED BY ACTIVE MYCOBACTERIUM AVIUM INFECTION SWITCH TO TH2 FOLLOWING CHALLENGE WITH SCHISTOSOMA MANSONI. Clinical Immunology. 2002. v. 104(3). p. 274-281. Interpretive Summary: Mycobacteria and worms induce very different immune responses. We were interested in determining how animals would respond if infected with mycobacteria and then later infected with a worm. Interestingly, the immune response to the worm prevailed over the response to the mycobacteria. Our work has important implications for clinical situations in which there is more than one organism affecting the host.
Technical Abstract: Mycobacterium avium established a systemic infection with non-caseating granulomatous inflammation in mice. Lymphocytes isolated from granulomas and exposed in vitro to PPD, elaborated IFN-gamma but little or no IL-4 or IL-5. In contrast, lymphocytes from hepatic granulomas of Schistosoma mansoni-infected mice stimulated with schistosome egg antigen, secreted IL- -4 and IL-5, but not IFN-gamma. Mice chronically infected with M. avium an subsequently co-infected with S. mansoni developed additional but morphologically distinct, hepatic granulomas in response to schistosome egg deposition. Schistosome eggs were not deposited in the spleen, and splenic granulomas in co-infected mice were induced by mycobacteria. In complete contrast to the TH1 cytokine pattern observed with granuloma lymphocytes from M. avium-infected mice, granuloma lymphocytes from co-infected mice stimulated with PPD elaborated IL-4, but not IFN-gamma. In addition, mycobacterial granulomas in concurrently infected mice contained large numbers of eosinophils, a feature never seen in granulomas of mice infected with M. avium alone. Serum IgG1 and IgE levels in concurrently infected mice were significantly higher, but IgG2a levels significantly lower than in M. avium-infected mice. These investigations show that an established TH1 response specific for M. avium becomes modified to a TH2 response after the host is subsequently infected with S. mansoni, a parasite that induces a strong TH2 response.