Old mice are able to control low-dose aerogenic infections with Mycobacterium tuberculosis.
Previous work in this laboratory has led to the development of the hypothesis that the increased susceptibility of old mice to tuberculosis infection reflects a limited ability by immune CD4 mediator cells to accumulate at sites of bacterial implantation. To test this hypothesis with very low dose infections, the present study documented the course of a low-dose aerogenic infection with virulent Mycobacterium tuberculosis Erdman against time in the target organs of young (3-month-old) and old (24-month-old) B6D2F1 hybrid mice. The results of the study indicated that the infection was controlled by the two groups of mice at similar rates, although the bacterial load in the old mice was eventually somewhat higher. Despite these similarities, some subtle differences between the young and old mice were also evident and included evidence of increased hematogenous spread of the infection from the lungs to other organs in the old mice. Interestingly, very poor expression of the cytokine interleukin-12 was observed in the lungs of infected old mice, leading to the hypothesis that the poor CD4 response in such animals could be partially attributed to the lack of this Th1-type, CD4 T-cell-enhancing cytokine. In this regard, treatment of old mice with exogenous interleukin-12 increased resistance and promoted gamma interferon secretion by CD4 T cells from these mice, although the effects were generally modest. These data suggest that old mice possess CD4-independent compensatory mechanisms by which to deal with low-dose pulmonary tuberculosis infections, although such mechanisms are less efficient than those seen in young animals.
Cooper
A M
AM
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
Callahan
J E
JE
Griffin
J P
JP
Roberts
A D
AD
Orme
I M
IM
D000332:Aerobiosis; D000375:Aging / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics; D018664:Interleukin-12 / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger; D018664:Interleukin-12