Gastric eosinophils are detrimental for Helicobacter pylori vaccine efficacy.

Details

Serval ID
serval:BIB_369D55787F13
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gastric eosinophils are detrimental for Helicobacter pylori vaccine efficacy.
Journal
Vaccine
Author(s)
Vaillant L., Oster P., McMillan B., Velin D.
ISSN
1873-2518 (Electronic)
ISSN-L
0264-410X
Publication state
Published
Issued date
16/06/2021
Peer-reviewed
Oui
Volume
39
Number
27
Pages
3590-3601
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Helicobacter pylori (Hp) colonizes the human gastric mucosa with a high worldwide prevalence. Currently, Hp can be eradicated by the use of antibiotics. Due to the increase of antibiotic resistance, new therapeutic strategies need to be devised: one such approach being prophylactic vaccination. Pre-clinical and clinical data showed that a urease-based vaccine is efficient in decreasing Hp infection through the mobilization of T helper (Th)-dependent immune effectors, including eosinophils. Preliminary data have shown that upon vaccination and subsequent Hp infection, eosinophils accumulate in the gastric mucosa, suggesting a possible implication of this granulocyte subset in the vaccine-induced reduction of Hp infection. In our study, we confirm that activated eosinophils, expressing CD63, CD40, MHCII and PD-L1 at their cell surface, infiltrate the gastric mucosa during vaccine-induced reduction of Hp infection. Strikingly, we provide evidence that bone marrow derived eosinophils efficiently kill Hp in vitro, suggesting that eosinophils may participate to the vaccine-induced reduction of Hp infection. However, conversely to our expectations, the absence of eosinophils does not decrease the efficacy of this Hp vaccine in vivo. Indeed, vaccinated mice that have been genetically ablated of the eosinophil lineage or that have received anti-Sialic acid-binding immunoglobulin-like lectin F eosinophil-depleting antibodies, display a lower Hp colonization when compared to their eosinophil sufficient counterparts. Although the vaccine induces similar urease-specific humoral and Th responses in both eosinophil sufficient and deficient mice, a decreased production of anti-inflammatory cytokines, such as IL-10, TGFβ, and calgranulin B, was specifically observed in eosinophil depleted mice. Taken together, our results suggest that gastric eosinophils maintain an anti-inflammatory environment, thus sustaining chronic Hp infection. Because eosinophils are one of the main immune effectors mobilized by Th2 responses, our study strongly suggests that the formulation of an Hp vaccine needs to include an adjuvant that preferentially primes Hp-specific Th1/Th17 responses.
Keywords
Animals, Eosinophils, Gastric Mucosa, Helicobacter Infections/prevention & control, Helicobacter pylori, Mice, Stomach, Th2 response, Vaccine
Pubmed
Web of science
Open Access
Yes
Create date
15/06/2021 8:17
Last modification date
12/08/2021 5:40
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