Role of TLR4 in the early response to Bordetella pertussis

AGUSTINA ERREA; GRISELDA MORENO; ROY ROBERTS; AUGUSTO GRAIEB; LAURY VAN MAELE; JEAN CLAUDE SIRARD; MARTIN RUMBO; ARNDT BENEKE; DANIELA HOZBOR

Valparaiso

Congreso; 9th Latin American Congress of Immunology, Viña del Mar, Chile November 3 – 7th 2009. XII Chilean Society of Immunology Congress. LVII Argentinean Society of Immunology Satellite Scientific Meeting.; 2009

In this study TLR4-dependent early response to Bordetella pertussis (Bp) infection was characterized. To this aim, transcriptional analysis after intranasal infection with Bp (108CFU/40μl) in TLR4 competent animals (C3HHeN) and TLR4 deficient (C3HHeJ) was performed using whole-genome coverage DNA microarrays. Genes differentially regulated (p<0.01) were classified by Ingenuity Pathway Analysis IPA® software. Two hours after infection differences between both strains were registered: while 205 genes, involved in biological process like cytokine and chemokine signalling/immunity, immunity and defense, and apoptosis inhibition were induced in the C3HHeN; only 7 genes were induced in C3HHeJ.  At 24 hs, despite both strains elicit a robust response (614 genes in CeHHeN vs 514 in C3HHeJ) C3HHeJ mice show a lower proinflamatory profile with greater number of modulatory genes induced and later and lower induction levels of the chemokine cluster. Concordantly, analysis of immune cell recruitment to airways showed a lesser and delayed influx of neutrophils in TLR4 deficient mice (9,6x105 ±1,6x105 total PMN in C3HHeN vs 1,4x105 ± 1,4x104 in C3HHeJ at 24 hs postinfection). Results indicate that TLR4 is critical in the early response to B. pertussis, particularly in the recruitment of cell populations necessary for the establishment of an effective response to anti-pertussis.