Neutrophils Exert a Suppressive Effect on Th1 Responses to Intracellular Pathogen Brucella abortus

PLoS Pathogens

Bernard Malissen¹  Edgardo Moreno¹  Vilma Arce-Gorvel¹  Anna Martirosyan²  Marie Malissen²  Alejandro Alfaro-Alarcón²  Hubert Lepidi³  Jean-Pierre Gorvel³  Diana Ordoñez-Rueda³  Elías Barquero-Calvo⁴ 

[1] Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France;Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, Marseille, France;Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France;Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica

关键词: Spleen;    Brucella;    Mouse models;    Cytokines;    Immune response;    Flow cytometry;    T cells;    Monocytes;   

DOI  :  10.1371/journal.ppat.1003167

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Polymorphonuclear neutrophils (PMNs) are the first line of defense against microbial pathogens. In addition to their role in innate immunity, PMNs may also regulate events related to adaptive immunity. To investigate the influence of PMNs in the immune response during chronic bacterial infections, we explored the course of brucellosis in antibody PMN-depleted C57BL/6 mice and in neutropenic mutant Genista mouse model. We demonstrate that at later times of infection, Brucella abortus is killed more efficiently in the absence of PMNs than in their presence. The higher bacterial removal was concomitant to the: i) comparatively reduced spleen swelling; ii) augmented infiltration of epithelioid histiocytes corresponding to macrophages/dendritic cells (DCs); iii) higher recruitment of monocytes and monocyte/DCs phenotype; iv) significant activation of B and T lymphocytes, and v) increased levels of INF-γ and negligible levels of IL4 indicating a balance of Th1 over Th2 response. These results reveal that PMNs have an unexpected influence in dampening the immune response against intracellular Brucella infection and strengthen the notion that PMNs actively participate in regulatory circuits shaping both innate and adaptive immunity.

【 授权许可】

CC BY