Dissemination of enteric Mycobacterium avium infections in mice rendered immunodeficient by thymectomy and CD4 depletion or by prior infection with murine AIDS retroviruses.
This study shows that infection of mice with the murine AIDS virus LP-BM5 or Du5H profoundly depressed the capacity of splenic T cells from these animals to respond to the T-cell mitogen phytohemagglutinin or concanavalin A or to alloantigens. Similar effects were also observed if mice were thymectomized and then infused with monoclonal anti-CD4 antibody (TxCD4- mice). When such mice were infected intravenously with Mycobacterium avium, growth of the infection was markedly exacerbated in the TxCD4- mice or in mice given murine AIDS virus 2 months earlier. In view of these data, we then investigated whether such treatments might cause dissemination of M. avium following enteric implantation of bacteria into the mouse cecum; this route was chosen in an attempt to model events in AIDS patients, in which the gut appears to be one of the major portals of M. avium infection. In this model, the entry and hematogenous dissemination of four clinical isolates of M. avium were monitored against time and found to be accelerated and enhanced in T-cell-deficient mice. In view of this finding, these novel approaches for enteric infection that use immunodeficient mice are presented as potential new models for the evaluation of immunotherapy and chemotherapy in a setting that bears some similarity to events believed to occur in AIDS patients.
Orme
I M
IM
Department of Microbiology, Colorado State University, Fort Collins 80523.
Furney
S K
SK
Roberts
A D
AD
D000818:Animals; D001853:Bone Marrow / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016867:Immunocompromised Host; D008168:Lung / Q000382:microbiology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000382:microbiology; D009164:Mycobacterium Infections / Q000276:immunology*; D009162:Mycobacterium avium / Q000254:growth & development / Q000472:pathogenicity*; D013154:Spleen / Q000382:microbiology; D013934:Thymectomy