TLR5-mediated activation of CD4+CD127+ innate immune cells expressing Th17–related cytokines protects against gut infection.

CARNOY CHRISTOPHE; LAURYE VAN MAELE; NATALIA MUÑOZ; ALEJANDRO CHABALGOITY; MARTIN RUMBO; WOLF HARDT; JEAN CLAUDE SIRARD

Viña del Mar, Chile.

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

<!-- /* 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;} --> <!-- /* Font Definitions */ @font-face {font-family:Times; panose-1:2 2 6 3 5 4 5 2 3 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:536902279 -2147483648 8 0 511 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:Times; mso-fareast-font-family:Times; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:EN-US;} p.MsoFooter, li.MsoFooter, div.MsoFooter {margin:0cm; margin-bottom:.0001pt; line-height:200%; mso-pagination:widow-orphan; tab-stops:center 216.0pt right 432.0pt; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:595.3pt 841.9pt; margin:35.45pt 70.85pt 70.85pt 70.85pt; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> The cytokines IL-17A, IL-17F, and IL-22 are produced during adaptive immunity by Th17 lymphocytes to stimulate innate antimicrobial defenses in mucosa. Here, we observed that systemic injection to mice of the TLR5 agonist flagellin induced the swift and transient Il17a, Il17f, and Il22 transcription in lymphoid tissues and throughout the intestine and the lung. This response enhanced expression of Th17-related genes involved in innate defenses. The spontaneous source of Th17-related cytokines was identified as a population of innate immune cells expressing the IL-7Ra chain (CD127) and CD4 similar to lymphoid tissue inducer (LTi)-like cells. Additionally, we noted that CD11c+ dendritic cells were essential to the immune activation. To test the contribution of the TLR5-stimulated CD4+CD127+ cells to mucosal immunity, we used a model of infection with Gram-negative bacterium Yersinia pseudotuberculosis that targets the small intestine. Pretreatment with flagellin conferred protection against oral infection independently of the IL-22 cytokine production. Interestingly, TLR4 signaling that stimulated Th17-related innate response in spleen, but not in the intestine, did not protect against Y. pseudotuberculosis infection. In summary, our results suggest that TLR5-induced production of Th17-related cytokines by CD4+CD127+ LTi-like cells is a major innate defense mechanism in response to gut invasion by flagellated microorganisms.