Nasal immunization with H7 flagellin protects mice against hemolytic uremic syndrome secondary to Escherichia coli O157:H7 gastrointestinal infection

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Agustina Juliana Errea¹  Martin Rumbo¹  Mónica Elba Vermeulen²  María Florencia Todero³  Daniela Romina Montagna⁴  María Victoria Ramos⁵  Romina Jimena Fernández-Brando⁵  Alan Mauro Bernal⁵  Fernando Nicolás Sosa⁵  Marina Sandra Palermo⁵ 

[1] Instituto de Estudios Inmunológicos y Fisiopatológicos - CONICET - Universidad Nacional de La Plata, La Plata, Argentina;Laboratorio de Células Presentadoras de Antígenos y Respuesta Inflamatoria, IMEX CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina;Laboratorio de Fisiología de Procesos Inflamatorios, IMEX CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina;Laboratorio de Oncología Experimental, IMEX CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina;Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Academia Nacional de Medicina, Buenos Aires, Argentina;

关键词: Escherichia coli;    intestinal infection;    HUS;    flagellin;    immunization;    mouse model;    immune-response;    Shiga toxin;   

DOI  :  10.3389/fcimb.2023.1143918

 received in 2023-01-13, accepted in 2023-04-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionShiga-toxin (Stx) producing Escherichia coli (STEC) O157:H7 is the most frequent serotype associated with hemolytic uremic syndrome (HUS) after gastrointestinal infections. Protection against HUS secondary to STEC infections has been experimentally assayed through the generation of different vaccine formulations. With focus on patients, the strategies have been mainly oriented to inhibit production of Stx or its neutralization. However, few approaches have been intended to block gastrointestinal phase of this disease, which is considered the first step in the pathogenic cascade of HUS. The aim of this work was to assay H7 flagellin as a mucosal vaccine candidate to prevent the systemic complications secondary to E. coli O157:H7 infections.Materials and methodsThe cellular and humoral immune response after H7 nasal immunization in mice were studied by the analysis of systemic and intestinal specific antibody production, as well as cytokine production and lymphocyte proliferation against H7 flagellin ex vivo.ResultsImmunized mice developed a strong and specific anti-H7 IgG and IgA response, at systemic and mucosal level, as well as a cellular Th1/Th2/Th17 response. H7 induced activation of bone marrow derived dendritic cells in vitro and a significant delayed-type hypersensitivity (DTH) response in immunized mice. Most relevant, immunized mice were completely protected against the challenge with an E. coli O157:H7 virulent strain in vivo, and surviving mice presented high titres of anti-H7 and Stx antibodies.DiscussionThese results suggest that immunization avoids HUS outcome and allows to elicit a specific immune response against other virulence factors.

【 授权许可】

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Copyright © 2023 Bernal, Sosa, Todero, Montagna, Vermeulen, Fernández-Brando, Ramos, Errea, Rumbo and Palermo