Activation of Human CD11b+ B1 B-Cells by Trypanosoma cruzi-Derived Proteins Is Associated With Protective Immune Response in Human Chagas Disease

Passos, Lívia Silva Araújo; Magalhães, Luísa Mourão Dias; Soares, Rodrigo P.; Marques, Alexandre F.; Alves, Marina Luiza Rodrigues; Giunchetti, Rodolfo Cordeiro; Nunes, Maria do Carmo Pereira; Gollob, Kenneth J.; Dutra, Walderez Ornelas

doi:10.3389/fimmu.2018.03015

Cited by 24 publications

(17 citation statements)

References 65 publications

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“…It has been suggested that the non‐specific polyclonal B‐cell activation contributes to delay the generation of T. cruzi ‐specific B‐cell responses, thus contributing to parasite escape and establishment of chronic infections 133,134 . Polyclonal B‐cell activation is associated with rapid, innate‐like production of IL‐17 and IL‐10 135,136 but the wider relevance is unclear as both protective 136‐138 and deleterious 51,52,135 roles for such innate‐like B‐cell responses have been documented in different models. The infection also causes a transient, yet marked loss of immature B cells in the bone marrow in experimental mouse models, possibly further compromising the response 139 …”

Section: Stage 2: Adaptive Responses Take Controlmentioning

confidence: 99%

“…B cells also produce IL‐10, 135 and overall IL‐10 production is lower in B1 B‐cell‐deficient mice early during infection 159 . CD11b + B1 B cells from asymptomatic, infected individuals show increased capacity to produce IL‐10 compared to those with cardiac disease symptoms 138 . In addition, recent data show that when compared to non‐infected donors, chronically T. cruzi ‐infected individuals with cardiac manifestations have an increased proportion of immature transitional CD24 high CD38 high and naïve B cells able to produce IL‐10 upon in vitro re‐stimulation 160 .…”

Section: Stage 2: Adaptive Responses Take Controlmentioning

confidence: 99%

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Host‐parasite dynamics in Chagas disease from systemic to hyper‐local scales

Pérez‐Mazliah

Ward

Lewis

2020

Parasite Immunology

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Trypanosoma cruzi is a remarkably versatile parasite. It can parasitize almost any nucleated cell type and naturally infects hundreds of mammal species across much of the Americas. In humans, it is the cause of Chagas disease, a set of mainly chronic conditions predominantly affecting the heart and gastrointestinal tract, which can progress to become life threatening. Yet around two thirds of infected people are long‐term asymptomatic carriers. Clinical outcomes depend on many factors, but the central determinant is the nature of the host‐parasite interactions that play out over the years of chronic infection in diverse tissue environments. In this review, we aim to integrate recent developments in the understanding of the spatial and temporal dynamics of T. cruzi infections with established and emerging concepts in host immune responses in the corresponding phases and tissues.

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Section: Stage 2: Adaptive Responses Take Controlmentioning

confidence: 99%

Section: Stage 2: Adaptive Responses Take Controlmentioning

confidence: 99%

Host‐parasite dynamics in Chagas disease from systemic to hyper‐local scales

Pérez‐Mazliah

Ward

Lewis

2020

Parasite Immunology

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“…In humans, circulating regulatory B10 results altered during the chronic stage and is associated with improved cardiac function in the indeterminate stage of Chagas disease ( Passos et al., 2019 ; Girard et al., 2021 ). Also, since we observed a regulatory phenotype on parasite-stimulated B cells we tested for the presence of IL-21, a cytokine related to regulatory B10 cell generation ( Horikawa et al., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi Induces B Cells That Regulate the CD4+ T Cell Response

Somoza

Bertelli

Pratto

et al. 2022

Front. Cell. Infect. Microbiol.

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Trypanosoma cruzi infection induces a polyclonal B cell proliferative response characterized by maturation to plasma cells, excessive generation of germinal centers, and secretion of parasite-unrelated antibodies. Although traditionally reduced to the humoral response, several infectious and non-infectious models revealed that B lymphocytes could regulate and play crucial roles in cellular responses. Here, we analyze the trypomastigote-induced effect on B cells, their effects on CD4+ T cells, and their correlation with in vivo findings. The trypomastigotes were able to induce the proliferation and the production of IL-10 or IL-6 of naïve B cells in co-culture experiments. Also, we found that IL-10-producing B220lo cells were elicited in vivo. We also found up-regulated expression of FasL and PD-L1, proteins involved in apoptosis induction and inhibition of TCR signaling, and of BAFF and APRIL mRNAs, two B-cell growth factors. Interestingly, it was observed that IL-21, which plays a critical role in regulatory B cell differentiation, was significantly increased in B220+/IL-21+ in in vivo infections. This is striking since the secretion of IL-21 is associated with T helper follicular cells. Furthermore, trypomastigote-stimulated B-cell conditioned medium dramatically reduced the proliferation and increased the apoptotic rate on CD3/CD28 activated CD4+ T cells, suggesting the development of effective regulatory B cells. In this condition, CD4+ T cells showed a marked decrease in proliferation and viability with marginal IL-2 or IFNγ secretion, which is counterproductive with an efficient immune response against T. cruzi. Altogether, our results show that B lymphocytes stimulated with trypomastigotes adopt a particular phenotype that exerts a strong regulation of this T cell compartment by inducing apoptosis, arresting cell division, and affecting the developing of a proinflammatory response.

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“…The heterogeneous immune response has been reported during infection with L. chagasi , where differential effects on B and T cells were noticed in three different experimental inbred mouse strain [ 38 ]. However, in human Chagas disease, B1 B cells play opposite role, where CD11b+ B1 B cells are responsible for protective immune response [ 39 ]. The interaction between L. donovani amastigotes and purified splenic B cell induces IL-10 secretion by MZ B cell and Breg B cells leading to disease exacerbation [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Splenic B Cell Subsets during Experimental Leishmania donovani Infection in BALB/c Mice

et al. 2021

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Sodium antimonials are one of the major and common drugs used against visceral form leishmaniasis (VL). However, the development of drug resistance makes it difficult to manage this disease. Current work investigates the modulation of splenic B cells during experimental infection with antimony-sensitive and -resistant Leishmania donovani infection. Here we phenotypically characterized splenic B cell subsets in BALB/c mice infected with antimony drug-sensitive and -resistant VL strains using flow-cytometry method. In the splenocytes we noticed increased number of Transitional T3 B cells and B1a B cells in drug-resistant VL strain infection. Besides, we also observed alteration in Follicular B cell population of antimony-resistant strain infected mice. Drug-resistant strain induced secretion of elevated level of IL-10 from B1a B cells and IL-6 from Transitional T3 B cell subsets in the splenocytes. Purified splenic B cells from antimony drug-resistant strain infected mice showed decrease in the Lyn kinase gene expression compared to sensitive strain infected and uninfected mice. The current study provides insight into changes in host splenic B-cell subsets during experimental infection with antimony-sensitive and -resistant L. donovani in murine model.

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Activation of Human CD11b+ B1 B-Cells by Trypanosoma cruzi-Derived Proteins Is Associated With Protective Immune Response in Human Chagas Disease

Cited by 24 publications

References 65 publications

Host‐parasite dynamics in Chagas disease from systemic to hyper‐local scales

Host‐parasite dynamics in Chagas disease from systemic to hyper‐local scales

Trypanosoma cruzi Induces B Cells That Regulate the CD4+ T Cell Response

Modulation of Splenic B Cell Subsets during Experimental Leishmania donovani Infection in BALB/c Mice

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