Toll- like receptor 4 orchestrates neutrophil recruitment into airways during the first hours of Bordetella pertussis infection

MORENO G; ERREA A; VAN MAELE L; ROBERTS R; LÉGER H; SIRARD JC; BENECKE A; RUMBO M; HOZBOR D

MICROBES AND INFECTION

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2013

1286-4579

Most of the knowledge on the impact of Bordetella pertussis lipo-oligosaccharide31 (LOS) on the infectious process was obtained when the bacteria was established within32 the host. The aim of the present work was to determine the role of TLR4 at a very early33 step of the infectious process. To this end we used a transcriptomic approach on B.34 pertussis intranasal infection model in C3H/HeN, a TLR4-competent mouse strain, and35 C3H/HeJ, a TLR4-deficient mouse strain. The expression of approximately 140 genes36 was significantly changed 2 h post-infection in the C3H/HeN animals compared to the37 C3H/HeJ animals, which were essentially non-responders at this early time point.38 Pathways specific for immunity and defense, chemokine- and cytokine-mediated39 functions and TLR signaling, were activated upon infection in the TLR4 competent40 mice either at 2 h or 24 h. Furthermore, we observed that TLR4 signaling is absolutely41 required to promote the rapid recruitment of neutrophils into the airways. Interestingly,42 the depletion of those neutrophils impacted on B. pertussis lung counts in the first three43 days, thereby exacerbating the lung infection. In summary, we determined that TLR4 is44 a central player in initial neutrophil recruitment and orchestration of the very early45 innate defense against B. pertussis.