Prolonged survival of scavenger receptor class A-deficient mice from pulmonary Mycobacterium tuberculosis infection.

The present study tested the hypothesis that the scavenger receptor SR-A modulates granuloma formation in response to pulmonary infection with Mycobacterium tuberculosis (MTB). To test this hypothesis, we monitored survival and histopathology in WT and SR-A-deficient mice following aerosol infection with MTB Rv. SR-A-deficient (SR-A-/-) mice infected with MTB survived significantly longer than WT mice; the mean survival of SR-A-/- mice exceeded 430 days compared to 230 days for WT mice. Early granuloma formation was not impaired in SR-A-/- mice. The extended survival of SR-A-/- mice was associated with 13- and 3-fold higher number of CD4+ lymphocytes and antigen presenting cells in SR-A-/- lungs compared to WT mice 280 after infection. The histopathology of chronically infected SR-A-/- lungs, however, was marked by abundant cholesterol clefts in parenchymal lesions containing infection in multinucleated giant cells. The present study indicates SR-A as a candidate gene of the innate immune system influencing the chronic phase of M. tuberculosis infection.