Role of TLR4 in the early response to Bordetella pertussis.

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

Viña del Mar, Chile.

Congreso; IX Congreso of the Latin American Association of Immunology; 2009

&amp;amp;amp;amp;amp;amp;lt;!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:ES-TRAD; mso-fareast-language:FR;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --&amp;amp;amp;amp;amp;amp;gt; <!-- /* Font Definitions */ @font-face {font-family:Tahoma; panose-1:2 11 6 4 3 5 4 4 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:1627421319 -2147483648 8 0 66047 0;} @font-face {font-family:"Century Gothic"; panose-1:2 11 5 2 2 2 2 2 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:647 0 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Century Gothic"; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:Arial;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} -->   In this study we aimed to enhance the knowledge about TLR4 dependent early response to Bordetella pertussis (Bp). For this purpose, TLR4 competent (C3HHeN) and TLR4 deficient mice (C3HHeJ) were intranasally infected with 108CFU of Tohama strain and 2 and 24hs postinfection lung’s gene-expression profiles were analysed using DNA microarrays covering all murine genome.Genes  differentially regulated  (p<0.01)  were classified by Ingenuity Pathway Análisis IPA® sotware. Differences between both mice were evident since the beginning of infection: whereas 205 genes, involved in biological process like cytokine and chemockine signalling/immunity, immunity and defense, and apoptosis inhibition were induced in the C3HHeN mice at 2 hs, only 7 were found for C3HHeJ mice. At 24 hs, despite both strains can elicit a robust response (614 genes in CeHHeN vs 514 in C3HHeJ) C3HHeJ mice shows a lower proinflamatory profile whit greater number of modulatory genes induced and a late and lower induction levels in the cluster of chemockines, clearly affecting CXCL1, CXCL2 y CXCL5. According to this, analysis of immune population recruitment to airways showed a lesser and delayed capacity to recruit neutrophils in TLR4 deficient mice (9,6x105 ±1,6x105 total PMN in C3HHeN vs 1,4x105 ± 1,4x104 in C3HHeJ at 24 hs postinfection) .Our results show that early anti Bp response is clearly dependent on TLR4 functionality, being the ability to recruit PMN an important step in the control of infection controlled by this innate receptor.