Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production

Flores‐Langarica, Adriana; Bobat, Saeeda; Marshall, Jennifer L.; Yam‐Puc, Juan Carlos; Cook, Charlotte N.; Serre, Karine; Kingsley, Robert A.; Flores‐Romo, Leopoldo; Uematsu, Satoshi; Akira, Shizuo; Henderson, Ian R.; Toellner, Kai‐Michael; Cunningham, Adam F.

doi:10.1002/eji.201545564

Cited by 23 publications

(25 citation statements)

References 48 publications

(73 reference statements)

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“…Flagellin was initially reported to stimulate Th1-type responses when administered by systemic route [46,47]. However, our observations and studies from Cunningham et al also support induction of Th2 responses against S. Typhimurium flagellin [16,48] (Figure 2).…”

supporting

confidence: 63%

Compartmentalized Antimicrobial Defenses in Response to Flagellin

Vijayan

Rumbo

Carnoy

et al. 2018

Trends in Microbiology

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Motility is often a pathogenicity determinant of bacteria targeting mucosal tissues. Flagella constitute the machinery that propels bacteria into appropriate niches. Besides motility, the structural component, flagellin, which forms the flagella, targets Toll-like receptor 5 (TLR5) to activate innate immunity. The compartmentalization of flagellin-mediated immunity and the contribution of epithelial cells and dendritic cells in detecting flagellin within luminal and basal sides are highlighted here, respectively. While a direct stimulation of the epithelium mainly results in recruitment of immune cells and production of antimicrobial molecules, TLR5 engagement on parenchymal dendritic cells can contribute to the stimulation of innate lymphocytes such as type 3 innate lymphoid cells, as well as T helper cells. This review, therefore, illustrates how the innate and adaptive immunity to flagellin are differentially regulated by the epithelium and the dendritic cells in response to pathogens that either colonize or invade mucosa.

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supporting

confidence: 63%

Compartmentalized Antimicrobial Defenses in Response to Flagellin

Vijayan

Rumbo

Carnoy

et al. 2018

Trends in Microbiology

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“…Therefore, in our model, it is possible that secretion from Salmonella enables ESAT-6 to suppress IFN-␥ production, while ESAT-6 immobilized on the cell surface is unable to impart this function. Such a modulation of Th1 responses to S. Typhimurium has been observed in mice coimmunized with S. Typhimurium and soluble FliC (44). Furthermore, since individual antigens expressed by S. Typhimurium can contain multiple epitopes (47), presentation of ESAT-6 as a secreted, soluble antigen rather than restricted on the bacterial cell surface may alter the availability of epitopes presented by antigenpresenting cells, thereby influencing the induction and phenotype of responsive T cells.…”

Section: Discussionmentioning

confidence: 99%

Controlled Human Malaria Infection: Applications, Advances, and Challenges

2018

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The use of recombinant attenuated Salmonella vaccine (RASV) strains is a promising strategy for presenting heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ on where heterologous antigens are expressed and localized within the bacterium, and it is unclear how antigen localization modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in cell culture supernatant. In the present study, this Pet system was used to express early secretory antigen 6 (ESAT-6), an immunodominant and diagnostic antigen from Mycobacterium tuberculosis, in Salmonella enterica serovar Typhimurium strain SL3261. Three strains were generated, whereby ESAT-6 was expressed as a cytoplasmic (SL3261/cyto), surface-bound (SL3261/surf), or secreted (SL3261/sec) antigen. Using these RASVs, the relationship between antigen localization and immunogenicity in infected C57BL/6 mice was systematically examined. Using purified antigen and specific tetramers, we showed that mice infected with the SL3261/surf or SL3261/sec strain generated large numbers of Th1 CD4 ϩ ESAT-6 ϩ splenic T cells compared to those of mice infected with SL3261/cyto. While all mice showed ESAT-6-specific antibody responses when infected with SL3261/surf or SL3261/sec, peak total serum IgG antibody titers were reached more rapidly in mice that received SL3261/sec. Thus, how antigen is localized after production within bacteria has a more marked effect on the antibody response than on the CD4 ϩ T cell response, which might influence the chosen strategy to localize recombinant antigen in RASVs.

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“…Recombinant soluble FliC protein with N-terminal His tag was purified by Ni-NTA chromatography (Flores-Langarica et al, 2015). Quantitative ELISA was used to analyze the antibody response according to the procedure described below.…”

Section: Methodsmentioning

confidence: 99%

Outer membrane vesicles derived from Salmonella Typhimurium mutants with truncated LPS induce cross-protective immune responses against infection of Salmonella enterica serovars in the mouse model

Liu

et al. 2016

International Journal of Medical Microbiology

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Salmonella enterica cause diarrheal and systemic diseases and are of considerable concern worldwide. Vaccines that are cross-protective against multiple serovars could provide effective control of Salmonella-mediated diseases. Bacteria-derived outer membrane vesicles (OMVs) are highly immunogenic and are capable of eliciting protective immune responses. Alterations in lipopolysaccharide (LPS) length can result in outer membrane remodeling and composition of outer membrane proteins (OMPs) changing. In this study, we investigated the impact of truncated LPS on both the production and immunogenicity of Salmonella OMVs, including the ability of OMVs to elicit cross-protection against challenge by heterologous Salmonella strains. We found that mutations in waaJ and rfbP enhanced vesiculation, while mutations in waaC, waaF and waaG inhibited this process. Animal experiments indicated that OMVs from waaC, rfaH and rfbP mutants induced stronger serum immune responses compared to OMVs from the parent strain, while all elicited protective responses against the wild-type S. Typhimurium challenge. Furthermore, intranasal or intraperitoneal immunization with OMVs derived from the waaC and rfbP mutants elicited significantly higher cross-reactive IgG responses and provided enhanced cross-protection against S. Choleraesuis and S. Enteritidis challenge than the wild-type OMVs. These results indicate that truncated-LPS OMVs are capable of conferring cross protection against multiple serotypes of Salmonella infection.

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Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production

Cited by 23 publications

References 48 publications

Compartmentalized Antimicrobial Defenses in Response to Flagellin

Compartmentalized Antimicrobial Defenses in Response to Flagellin

Controlled Human Malaria Infection: Applications, Advances, and Challenges

Outer membrane vesicles derived from Salmonella Typhimurium mutants with truncated LPS induce cross-protective immune responses against infection of Salmonella enterica serovars in the mouse model

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