title: IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response.
abstract: During chronic infection with Mycobacterium tuberculosis (Mtb), bacilli multiplication is constrained within lung granulomas until excessive inflammation destroys the lung. Neutrophils are recruited early and participate in granuloma formation, but excessive neutrophilia exacerbates the tuberculosis disease. Neutrophils thus appear as potential targets for therapeutic interventions, especially in patients for whom no antibiotic treatment is possible. Signals that regulate neutrophil recruitment to the lung during mycobacterial infection need to be better understood. We demonstrated here, in the mouse model, that neutrophils were recruited to the lung in two waves after intranasal infection with virulent Mtb or the live attenuated vaccine strain Bacillus Calmette Guérin (BCG). A first wave of neutrophils was swiftly recruited, followed by a subsequent adaptive wave that reached the lung together with IFN-γ- and IL-17A-producing T cells. Interestingly, the second neutrophil wave did not participate to mycobacteria control in the lung and established contacts with T cells. The adaptive wave was critically dependent on the expression of IL-17RA, the receptor for IL-17A, expressed in non-hematopoietic cells. In absence of this receptor, curtailed CXCL-1 and 5 production in the lung restrained neutrophil recruitment. CXCL-1 and 5 instillation reconstituted lung neutrophil recruitment in BCG-infected IL17RA-/- mice.
authors.affiliation: INRA, Université de Tours, UMR 1282, Infectiologie et Santé Publique, Nouzilly, France.
authors.forename: Robin
authors.initials: R
authors.lastname: Lombard
authors.affiliation: INRA, Université de Tours, UMR 1282, Infectiologie et Santé Publique, Nouzilly, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Doz
authors.affiliation: INRA, Université de Tours, UMR 1282, Infectiologie et Santé Publique, Nouzilly, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Carreras
authors.affiliation: INRA, Université de Tours, UMR 1282, Infectiologie et Santé Publique, Nouzilly, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Epardaud
authors.affiliation: INRA, Université de Tours, UMR 1282, Infectiologie et Santé Publique, Nouzilly, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Vern
authors.affiliation: INRA, Université de Tours, UMR 1282, Infectiologie et Santé Publique, Nouzilly, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Buzoni-Gatel
authors.affiliation: INRA, Université de Tours, UMR 1282, Infectiologie et Santé Publique, Nouzilly, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D054360:Chemokine CXCL1 / Q000276:immunology*; D054365:Chemokine CXCL5 / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D053722:Receptors, Interleukin-17 / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D001500:BCG Vaccine; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; C491673:Il17ra protein, mouse; D053722:Receptors, Interleukin-17