The role of Mal in alveolar macrophage-mediated resistance to Bordetella pertussis

Abstract

There is a global resurgence in pulmonary infection with Bordetella pertussis, the causative agent of whooping cough. B. pertussis is known to encode a number of virulence factors, some of which can function as pathogen-associated molecular patterns, including the Toil-like receptor 4 (TLR4) agonist, lipopolysaccharide, and lipopeptides that could be detected by TLR2. MyD88 adaptor-like protein (Mal; also known as Tirap) is an important TIR domain-containing TLR adaptor that connects TLR2 and TLR4 to the transcriptional activation of various antibacterial genes, including those encoding proinflammatory cytokines. TLR4- defective C3HeJ mice are more susceptible to infection with B. pertussis, with higher colonisation of bacteria in the lungs. Neither Mal -/- mice nor other TLR adaptor-defective mice have been infected with B. pertussis, and the pathogenesis of severe B. pertussis infection has not been completely characterised. Furthermore, Mal is now recognised to contribute to MyD88-independent and TLR4-independent signalling pathways.