The Generation of Regulatory B Cells by Helminth Parasites

Khan, Adnan; Amu, Sylvie; Saunders, Sean P.; Fallon, Padraic G.

doi:10.1007/978-1-4939-1161-5_11

Cited by 14 publications

(12 citation statements)

References 25 publications

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“…Splenic CD19 + CD1d hi B cells are expanded in mice infected with S. mansoni [19]. These helminth-generated B cells have similar characteristics to other reported regulatory B cells [9,20,21].…”

Section: Preferential Upregulation Of Tlr7 On Cd19 + Cd1d Hi B Cells supporting

confidence: 71%

Ligation of TLR7 on CD19⁺CD1d^hi B cells suppresses allergic lung inflammation via regulatory T cells

et al. 2015

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Eur. J. Immunol. 2015Immunol. . 45: 1842Immunol. -1854 Leukocyte signaling 1843 IntroductionA subset of B cells that has garnered intense interest are regulatory B (Breg) cells [1][2][3][4]. These include B cells that produce the anti-inflammatory cytokine IL-10, termed B10 cells [5][6][7], including murine CD19 + CD1d hi CD5 + B cells [8,9]. However, there is still no universally recognized phenotype for these cells. In naïve mice, Breg cells that secrete IL-10 exist as no more than 1-2% of all B220 + cells [8,10] with such IL-10-secreting B cells potently suppressing inflammation in several murine disease models [10][11][12][13][14] and have been shown to have effects in man [14]. Specific factors and mechanisms that induce or regulate Breg cells in vivo have recently been explored. We have previously demonstrated that helminths can expand a Breg-cell population that can suppress in allergic inflammatory conditions in mice in an IL-10-dependent manner [10,11]. Given that helminths can generate IL-10-producing Breg cells in both mouse and man [10,11,15], it is important to understand and define noninfective mechanisms by which to generate such cells both in vitro and in vivo [9]. Paradigm shifts in the role of B cells have described their effects in both innate and adaptive arms of the immune response [2,[16][17][18]. In particular, engagement of Toll-like receptors (TLR) on B cells can produce a plethora of cytokine responses [18].In order to gain further insight into the function of IL-10-secreting B cells in mice, we undertook RNA microarray analysis of Breg cells from helminth-infected mice and compared its gene expression profile with that of B cells from both infected and uninfected animals. On analysis, we discovered that Breg cells from Schistosoma mansoni infected mice contained upregulated expression of genes associated with pattern recognition of bacteria and viruses. Of particular significance was the elevated expression of the endosomal-resident TLR, Tlr7.Previously, we have shown that helminth-derived, IL-10-producing B cells can mediate airway hyperresponsiveness (AHR) through the induction of CD4 + FoxP3 + regulatory T (Treg) cells [10]. Here, we now demonstrate that TLR7 is expressed on CD19 + CD1d hi B cells and that agonism of this receptor can induce IL-10 production, both in vitro and in vivo. Furthermore, using adoptive transfer strategies we describe how these TLR7-elicited CD19 + CD1d hi B cells facilitate the suppression of AHR in mice through the induction of lung-resident Treg cells. We also indicate that these ligands can generate IL-10-secreting B cells in man, thus supplementing the current evidence base that TLR7 has the potential to be a therapeutic target in respiratory disease and providing novel insight into IL-10-producing Breg cell function. ResultsPreferential upregulation of Tlr7 on CD19 + CD1d hi B cells determined using helminth-infected mice Splenic CD19 + CD1d hi B cells are expanded in mice infected with S. mansoni [19]. These helminth-generated B cells have similar...

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Section: Preferential Upregulation Of Tlr7 On Cd19 + Cd1d Hi B Cells supporting

confidence: 71%

Ligation of TLR7 on CD19⁺CD1d^hi B cells suppresses allergic lung inflammation via regulatory T cells

et al. 2015

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“…A Puerto Rican strain of S. mansoni was maintained by passage in BALB/c strain mice and albino Biomphalaria glabrata snails, as previously described (27). Conventional mixed male and female (MF) sex infections of mice involved use of cercariae shed from infected snails.…”

Section: Methodsmentioning

confidence: 99%

Schistosoma mansoni Worm Infection Regulates the Intestinal Microbiota and Susceptibility to Colitis

et al. 2019

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Infection with parasite helminths induces potent modulation of the immune system of the host. Epidemiological and animal studies have shown that helminth infections can suppress or exacerbate unrelated autoimmune, allergic, and other inflammatory disorders. There is growing evidence that helminth infectionmediated suppression of bystander inflammatory responses is influenced by alterations in the intestinal microbiome modulating metabolic and immune functions of the infected host. We analyzed the fecal microbiota of mice infected with adult male Schistosoma mansoni worms, which are less susceptible to experimental colitis, and male-and female-worm-infected mice, which are highly sensitive to colitis. While both groups of infected mice developed a disrupted microbiota, there were marked alterations in mice with male and female worm infections. Antibiotic-treated recipients that were cohoused with both types of S. mansoni worm-infected mice acquired a colitogenic microbiome, leading to increased susceptibility to experimental colitis. Following anthelmintic treatment to remove worms from worm-only-infected mice, the mice developed exacerbated colitis. This study provides evidence that adult male S. mansoni worm infection modulates the host's immune system and suppresses bystander colitis while limiting dysbiosis of the host's intestinal microbiome during infection.

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“…Apart from secreted cytokines, other molecules have been associated with B REG -mediated suppressive effects. These include the membrane-associated molecules such as CD19 [13], CD62L and MHC-II [14], fas ligand [15], T-cell immunoglobulin and mucin domain [16], and programmed death ligand 1 [8,[17][18][19][20], as well as the intracellular signalling molecules signal transducer and activator of transcription 3 and myeloid differentiation response gene 88 [21].…”

Section: Suppressive Mechanisms Of Regulatory B Cellsmentioning

confidence: 99%

The role of regulatory B cells in allergen immunotherapy

Veen

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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The Generation of Regulatory B Cells by Helminth Parasites

Cited by 14 publications

References 25 publications

Ligation of TLR7 on CD19⁺CD1d^hi B cells suppresses allergic lung inflammation via regulatory T cells

Ligation of TLR7 on CD19⁺CD1d^hi B cells suppresses allergic lung inflammation via regulatory T cells

Schistosoma mansoni Worm Infection Regulates the Intestinal Microbiota and Susceptibility to Colitis

The role of regulatory B cells in allergen immunotherapy

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The Generation of Regulatory B Cells by Helminth Parasites

Cited by 14 publications

References 25 publications

Ligation of TLR7 on CD19+CD1dhi B cells suppresses allergic lung inflammation via regulatory T cells

Ligation of TLR7 on CD19+CD1dhi B cells suppresses allergic lung inflammation via regulatory T cells

Schistosoma mansoni Worm Infection Regulates the Intestinal Microbiota and Susceptibility to Colitis

The role of regulatory B cells in allergen immunotherapy

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Ligation of TLR7 on CD19⁺CD1d^hi B cells suppresses allergic lung inflammation via regulatory T cells

Ligation of TLR7 on CD19⁺CD1d^hi B cells suppresses allergic lung inflammation via regulatory T cells