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Impact of IL-17RA on neutrophil recruitment to the lung following infection with mycobacteria
Robin Lombard, Emilie Doz-Deblauwe, Florence Carreras, Fanny Bauchet, Dominique Buzoni-Gatel, Nathalie Winter
To cite this version:
Robin Lombard, Emilie Doz-Deblauwe, Florence Carreras, Fanny Bauchet, Dominique Buzoni-Gatel, et al.. Impact of IL-17RA on neutrophil recruitment to the lung following infection with mycobac- teria. Tuberculosis 2012: Biology, pathogenesis, intervention strategies, Sep 2012, Paris, France.
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Session #3 P299
Impact of IL-17RA on neutrophil recruitment to the lung following infection with mycobacteria
R. Lombard, E. Doz, F. Carreras, F. Bauchet, D. Buzoni-Gatel and N. Winter
INRA, Universite´ de Tours, UMR12, Centre de Tours, 37380 Nouzilly, France obin.lombard@tours.inra.fr
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The hallmark of Mycobacterium tuberculosis (Mtb) infection in the lung is the granuloma where several cell types cooperate to restrict bacilli multiplication. Granulomas are also inflammatory sites that must be controlled to avoid tissue damage. Among cells present in granulomas, neutrophils may play beneficial or detrimental roles [1]. Recently a new concept of IL-10 producing suppressive neutrophil has emerged that may contribute to mycobacterial pathogenesis [2]. The inflammatory cytokine IL-17A plays key roles in neutrophil recruitment in bacterial and fungal infections. Moreover, in the mouse model, IL-17A is involved in mature granuloma formation both after Mtb and M. bovis Bacillus Calmette-Guerin (BCG) infection [3,4]. IL-17RA is the common receptor for four members of the IL-17 cytokines family including the best characterized IL-17A. We decided to decipher its role in neutrophil recruitment to the lung and granuloma control in response to mycobacteria. Using flow cytometry, we observed neutrophils (CD11b+, Ly-6C+, Ly-6G+) recruited to the lung after intranasal BCG instillation. Neutrophil recruitment occurred in two peaks, a first innate from day 1 to 3 and a second adaptive correlating with the recruitment of CD4 T cells to the lung around day 23. Both IFN- and IL-17A were observed at this time point.
Interestingly, in IL-17RA -/- mice neutrophil recruitment was barely detected in the adaptive phase, whereas innate neutrophils were present. In vitro total lung cells stimulated with BCG produced IL- 10. However, IL-10 production was impaired in IL-17RA -/- mice during the adaptive phase.
This correlated with an increased production of IL-17A. We are currently characterizing chemokines involved in neutrophil recruitment during both phases of the immune response. We are also comparing granuloma formation in IL-17RA-/- versus wild type mice. In conclusion, during BCG infection, neutrophils peak in the lung at two distinct time points of the immune response. IL-17RA is a major regulator of neutrophil recruitment in the adaptive phase only suggesting that different signals or different neutrophils are present during the two phases.
We are currently deciphering whether IL-10 producing
suppressive neutrophils are recruited during granuloma maturation where they could dampen the host response and control bacteria.
1. Martino A, Badell E, Winter N (2011) Neutrophils in mycobacterial infections. In: Tacchini-Cottier F, van Zandbergen G, editors. Neutrophils In Infectious Diseases: Bentham Science publishers Ltd. pp. 42-48.
2. Zhang X, Majlessi L, Deriaud E, Leclerc C, Lo-Man R (2009) Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. 31: 761-771. 3. Okamoto Yoshida Y, Umemura M, Yahagi A, O’Brien RL, Ikuta K, et al. (2010) Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung. J Immunol 184: 4414-4422. 4.
Umemura M, Yahagi A, Hamada S, Begum MD, Watanabe H, et al. (2007) IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis Bacille Calmette- Guerin infection. J Immunol 178: 3786-3796.
P293 Identification of Host Signalling Intermediates Regulating Mycobacterium tuberculosis Intracellular Survival Using a Library of Novel Kinase In- hibitors
C. Korbee, M. Haks, N. Savage, J. Neefjes, H. Overkleeft and T. Ottenhoff
P294 Product Development Research Resources: U.S. National Institute of Al- lergy and Infectious Diseases
B. Laughon, L. Lanning and C. Sizemore
P295 In vitro combination studies of benzothiazinone lead compound against My- cobacterium tuberculosis
B. Lechartier, R. Hartkoorn and S. Cole
P296 A Mathematical Model of Early Interaction between Mycobacterium tuber- culosis and Macrophages
E. Pienaar and M. Lerm
P297 Early PET-CT changes during M. tuberculosis infection can predict infection T. Coleman, T. Rutledge, J. Tomko, D. Fillmore, L.J. Frye, J. Flynn and P. Lin P298 The Value of in Vitro Interferon-Gamma-Release Assay for Differential Diag-
nosis Between Intestinal Tuberculosis and Crohns Disease J. Liu, Y. Long, S. Lei and X. Hao
P299 Impact of IL-17RA on neutrophil recruitment to the lung following infection with mycobacteria
R. Lombard, E. Doz, F. Carreras, F. Bauchet, D. Buzoni-Gatel and N. Winter P300 Empowering macrophages to overpower Mycobacterium tuberculosis in a
battle for survival
S. Mahajan, V. Chandra, S. Dave, H.K. Dkhar, R. Nanduri, A. Saini, E. Raj and P.
Gupta
P301 New putative eukaryotic substrates of the tyrosine phosphatase PtpA from M. tuberculosis.
M. Margenat, L. Rodr´ıguez, A.-M. Labandera, M.M. Portela, R. Dur ´an, A.-M. Fer- reira and A. Villarino
P302 TPL2-ERK signalling promotes host resistance against Mycobacterium tu- berculosis infection
F. McNab, J. Ewbank, R. Rajsbaum, E. Stavropoulos, P. Redford, X. Wu, C. Gra- ham, M. Saraiva, G. Kallenius, P. Tsichlis, D. Chaussabel, S. Ley and A. O’Garra P303 Virulence-Specific Perturbations Induced in Host Cell Metabolic Pathways
by Mycobacterium tuberculosis.
P. Mehrotra, S. Jamwal, N.M. Saquib, V. Manivel and K. Rao
ORGANISING COMMITTEE
Pedro ALZARI (Paris), Marco BELLINZONI (Paris), Roland BROSCH (Paris), Carmen BUCHRIESER (Paris), Laleh MAJLESSI (Paris), and Ludovic TAILLEUX (Paris)
SCIENTIFIC COMMITTEE
Pedro ALZARI (IP, Paris), Clifton BARRY (NIAID, NIH, Bethesda), Roland BROSCH (IP, Paris), Stewart COLE (EPFL, Lausanne), Sabine EHRT (Cornell University, New York), Laurent FRAISSE (Sanofi‐Aventis, Toulouse), Brigitte GICQUEL (IP, Paris), and Valerie MIZRAHI (MRC, University of Cape Town)
THEME OF THE CONFERENCE
The EMBO conference series "Tuberculosis 2012" is an international congress on Tuberculosis and its causative organism Mycobacterium tuberculosis to be held from September 11‐15, 2012 at the Conference Centre of the Institut Pasteur, Paris.
Institut Pasteur
Centre d’Information Scientifique 25‐28 rue du Dr Roux 75724 Paris cedex 15 ‐ France http://www.pasteur.fr/tuberculosis2012
tuberculosis2012@pasteur.fr
