Small intestinal mucosa-associated lymphoid tissue lymphoma with deep ulcer and severe stenosis: A case report

Yoshimura, Kosuke; Ohge, Hiroki; Uegami, Shinnosuke; Watadani, Yusuke; Hirano, Toshinori; Takahashi, Shinya

doi:10.1016/j.ijscr.2021.106539

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…It is known that eosinophils prevent auto-inflammatory disorders on the mucosal surfaces, such as inflammatory bowel syndrome in the guts 25,26 by secreting Interleukin-1 receptor antagonist (IL1RA) 27-29 , Program death ligand 1 (PD-L1) 17,22 , and Indoleamine 2,3-dioxygenase (IDO) 13,30 . Based on the differences identified in the cytokine profile, we hypothesized that RB50 might promote the expression of one of these molecules, to suppress the secretion of IL17 by eosinophils.…”

Section: Resultsmentioning

confidence: 99%

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BordetellaSpp. Utilize T3SS To Promote Secretion of IL1RA Leading to Long-Term Persistent Infections

Williams

Roan

First

et al. 2022

Preprint

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A common feature of pathogens is their ability to suppress host immune responses. Understanding the molecular mechanisms and the common pathways that bacteria utilize to block host immune signaling cascade might provide novel avenues for vaccine and therapeutic development. Preventable infectious diseases remain one of the major causes of morbidity and mortality worldwide and the current rise in antibiotic resistance is increasing this burden. Bordetella spp. are respiratory pathogens that cause the long-term illness known as whoop-ing cough. Bordetella infections cause over 150,000 deaths each year, despite a vaccine be-ing available. In our studies, we used the mouse pathogen B. bronchiseptica to investigate the pneumonic stage of disease, which very well mimics the fatal disease caused by B. pertussis. In our previous work we discovered a B. bronchiseptica mutant, RB50DbtrS, that clears rapidly from the lungs of mice and generates protective immunity that lasts for at least 15 months post-challenge. Combining the mouse immunological tools and both bacteria, the wildtype RB50 and mutant RB50DbtrS, which persists for up to 56 days and clears in 14-21 days, respectively, we investigated the mechanisms by which the wildtype B. bronchiseptica blocks host immune response to cause long term lung infection. Previous research indicated eosinophils as critical for rapid clearance of the mutant bacteria from the lungs. In vitro assays with eosinophils demonstrated that the RB50DbtrS mutant strain promotes the secretion of pro-inflammatory signals. In contrast, infection of eosinophils with RB50 promoted the se-cretion of anti-inflammatory signals such as IL1RA. Interestingly, IL1RA was also increased in the lungs of mice infected with the wildtype but not with the mutant RB50 strain. Infection with RB50DbscN, which lacks a functional type 3 secretion system (T3SS), was sufficient to prevent IL1RA induction suggesting that the bacterial effector responsible for IL1RA upregula-tion is a substrate of the T3SS. Supplementation with IL1RA after infection with RB50 or RB50DbtrS resulted in increased lung bacterial burden for both bacterial strains. However, more rapid clearance of RB50 was observed after infection of mice in which IL1RA was knocked out. Furthermore, anti-IL1RA antibody treatment promoted rapid clearance of not only RB50 but also the human pathogens B. pertussis and B. parapertussis. This suggests that IL1RA may be a promising therapeutic target to treat severe cases of whooping cough. Overall, this work demonstrates that Bordetella spp. induces IL1RA expression to promote persistence using the T3SS. Since other bacteria have also been shown to target IL1RA, this may be a conserved bacterial mechanism to promote host-immune suppression.

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Section: Resultsmentioning

confidence: 99%

Section: Rb50 Promotes Il1ra Expression In Eosinophilsmentioning

confidence: 99%

BordetellaSpp. Utilize T3SS To Promote Secretion of IL1RA Leading to Long-Term Persistent Infections

Williams

Roan

First

et al. 2022

Preprint

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“…Eosinophils not only have antibacterial activities themselves, but also they play important roles during the maintenance of mucosal responses 19 , due to their intrinsic relationship with lymphocites 53 , 60 , 61 . Moreover, their involvement during the formation 62,63 and maintenance 28 of mucosal associated lymphoid tissue is currently now elucidated. Due to their critical and important roles in maintaining the balance between anti-and auto-inflammatory responses, it makes sense that bacteria target these cells to prevent the generation of robust immune responses and protective immunity that allow not only for increased persistence but also reinfection.…”

Section: Discussionmentioning

confidence: 99%

Bordetella spp. block eosinophil recruitment to suppress lung iBALT formation

First¹,

Martínez²,

González‐Fernández³

et al. 2022

Preprint

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A characteristic that differentiates pathogenic and opportunistic bacteria is that pathogens have been selected by their ability to suppress host inflammatory responses allowing colonization and persistence. Bordetella spp. are respiratory pathogens characterized for the arsenal of mechanisms they use to manipulate host immune responses. We have previously characterized a B. bronchiseptica mutant, RB50DbtrS, that is not able to suppress host immune responses, resulting not only in rapid clearance of the infection but also long-term lung sterilizing immunity against reinfection with the three classical Bordetella spp. Interestingly, this strong immune response requires eosinophils. In this work our results indicate that wildtype B. bronchiseptica, RB50, blocks eosinophil pro-inflammatory functions to prevent the rapid recruitment of B and T cells to the lung that results in iBALT formation. Moreover, eosinophils promote a TH17 microenvironment within the iBALT that might be responsible for the long-term robust protective immunity generated by infection with this mutant. Overall, this work provides a novel role for eosinophils as promoters of adaptive immune responses and protective immunity, while also indicating that bacteria actively manipulate those cells to promote long-term persistence and reinfection.

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Bordetella spp. block eosinophil recruitment to suppress the generation of early mucosal protection

First,

Parrish,

Martínez-Pérez

et al. 2023

Cell Reports

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Small intestinal mucosa-associated lymphoid tissue lymphoma with deep ulcer and severe stenosis: A case report

Cited by 3 publications

References 7 publications

BordetellaSpp. Utilize T3SS To Promote Secretion of IL1RA Leading to Long-Term Persistent Infections

BordetellaSpp. Utilize T3SS To Promote Secretion of IL1RA Leading to Long-Term Persistent Infections

Bordetella spp. block eosinophil recruitment to suppress lung iBALT formation

Bordetella spp. block eosinophil recruitment to suppress the generation of early mucosal protection

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