MyD88-Deficient Mice Display a Profound Loss in Resistance toMycobacterium tuberculosisAssociated with Partially Impaired Th1 Cytokine and Nitric Oxide Synthase 2 Expression

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Abstract
Mycobacterium tuberculosispossesses agonists for several Toll-like receptors (TLRs), yet mice with single TLR deletions are resistant to acute tuberculosis. MyD88−/−mice were used to examine whether TLRs play any role in protection against aerogenicM. tuberculosisH37Rv infection. MyD88−/−mice failed to control mycobacterial replication and rapidly succumbed. Moreover, expressions of interleukin 12, tumor necrosis factor alpha, gamma interferon, and nitric oxide synthase 2 were markedly decreased in the knockout animals. These results argue that resistance toM. tuberculosismust depend on MyD88-dependent signals mediated by an as-yet-undetermined TLR or a combination of TLRs.