CHEMOKINE RESPONSE IN MICE INFECTED WITH MYCOBACTERIUM-TUBERCULOSIS

We show here that infection of murine macrophages with various strains of Mycobacterium tuberculosis induces the rapid in vitro expression o f genes encoding chemokines macrophage inflammatory protein Icu and ma crophage inflammatory protein 2, which recruit neutrophils to sites of infection, and macrophage-recruiting chemokines 10-kDa, interferon-in ducible protein (IP-10) and macrophage chemotactic protein 1. Three st rains of M. tuberculosis, Erdman and the clinical isolates CSU 22 and CSU 46, induced similar levels of secretion of macrophage chemotactic protein 1 from infected macrophage monolayers; however, the Erdman str ain failed to induce levels of secretion of tumor necrosis factor alph a similar to those induced by either CSU 22 or CSU 46. Using a low-dos e aerosol infection model, we also found that while the Erdman strain induced negligible increases in chemokine mRNA levels in the lungs, in fection with either CSU 22 or CSU 46 resulted in greater levels of mRN A production for all four chemokines tested. The growth of these strai ns in the lungs was, however, equally well contained by acquired host immunity. These data allow us to hypothesize that the chemokine respon se in the lungs probably does not control the protective granulomatous response and that perhaps other T-cell- or macrophage-associated cyto kines such as tumor necrosis factor alpha or interleukin 12 may be inv olved in this process.