Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection

Rolot, Marion; Dougall, Annette M.; Chetty, Alisha; Javaux, Justine; Chen, Ting; Xiao, Xue; Machiels, Bénédicte; Selkirk, Murray E.; Maizels, Rick M.; Hokke, Cornelis H.; Denis, Olivier; Brombacher, Frank; Vanderplasschen, Alain; Gillet, Laurent; Horsnell, William G. C.; Dewals, Benjamin G

doi:10.1038/s41467-018-06978-5

Cited by 80 publications

(83 citation statements)

References 59 publications

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“…12,14,15 Given the pivotal role of IL-15 in T VM -cell generation, high expression of IL-15Rb and Eomes can be used as additional phenotypic markers of T VM cells. 12 While nonredundant roles in T VM -cell generation are not observed for other common-gamma chain (cc) cytokines, IL-4 signaling can expand T VM -cell populations 1,12,16,17 and T VM cells express and maintain high levels of the IL-7a chain (CD127), 13 which is consistent with a role in their survival.…”

Section: Introductionmentioning

confidence: 90%

“…T VM cells bridge the gap between innate and adaptive immunity, providing both innate‐like and memory‐like functionality during this period of immunological vulnerability. Indeed, T VM cells are crucial for generation of rapid protective immunity in vivo in a number of bacterial and viral models . T VM cells are therefore proposed to provide an additional layer of heterogeneity within naïve CD8 T‐cell populations, ensuring that antigen‐naïve CD8 T cells are intrinsically diverse with regard to both (1) antigen specificity based on TCR expression and (2) preprogrammed response kinetics and functionality based on their IL‐15‐driven differentiation state …”

Section: Refining the Model Of Tvm‐cell Generationmentioning

confidence: 99%

“…IL‐4 signaling also augments T VM ‐cell generation and may positively regulate IL‐15 signaling. Ablation of IL‐4 or its receptor leads to a modest decrease in the frequency of T VM cells, while IL‐4 production during helminth infection increases the frequency of T VM cells . In addition, the development of a population of T MP cells, known as innate memory CD8 T (T IM ) cells is dependent on IL‐4 but not IL‐15 (Table ) (reviewed in).…”

Section: Integration Of Il‐15 Ifn Il‐4 and Tcr Signaling Pathways Imentioning

confidence: 99%

“…While the cumulative impact of multiple infections on T VM ‐cell homeostasis has not been defined, it is well established that viral infections can cause expansion of T MP and presumably T VM cells . In addition, a single infection with helminths was sufficient to increase T VM ‐cell frequency in the periphery, in an IL‐4 dependent manner, leading to more effective clearance of subsequent murid gammaherpesvirus 4 infection or listerial infection . This illustrates that pathogenic exposures have a significant acute impact on T VM ‐cell homeostasis and function but the long‐term impact of such exposures remains to be characterized.…”

Section: Maintenance Of Tvm Cells and The Impact Of Infection And Agingmentioning

confidence: 99%

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Similar but different: virtual memory CD8 T cells as a memory‐like cell population

Hussain

Quinn

2019

Immunol Cell Biol

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Immunological memory is a phenomenon where the immune system can respond more rapidly to pathogens and immunological challenges that it has previously encountered. It is defined by several key hallmarks. After an initial encounter, immune cells (1) expand and (2) differentiate to form memory cell populations. Memory cells are (3) long‐lived and (4) facilitate more rapid immune responses to subsequent infection because of (i) an increase in cell number, (ii) a decrease in the signaling threshold required for entry into cell cycle or effector function and (iii) localization of cells to tissue sites for surveillance. Classically, immunological memory has been antigen specific but it is becoming apparent that mechanisms of immunological memory can be co‐opted by innate or antigen‐inexperienced immune cells to generate heterogeneity in immune responses. One such cell is the virtual memory CD8 T (TVM) cell, which is a semi‐differentiated but antigen‐naïve CD8 T‐cell population. This review will summarize current knowledge of how TVM cells are generated, their memory‐like hallmarks, how they are maintained during steady state, infection and aging, and propose a model to integrate key signaling pathways during their generation.

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Section: Introductionmentioning

confidence: 90%

Section: Refining the Model Of Tvm‐cell Generationmentioning

confidence: 99%

Section: Integration Of Il‐15 Ifn Il‐4 and Tcr Signaling Pathways Imentioning

confidence: 99%

Section: Maintenance Of Tvm Cells and The Impact Of Infection And Agingmentioning

confidence: 99%

See 2 more Smart Citations

Similar but different: virtual memory CD8 T cells as a memory‐like cell population

Hussain

Quinn

2019

Immunol Cell Biol

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“…Because IL-4/IL-13 or M2a polarization is shown to play a clear role in other disease states and is likely to be relevant to a variety of helminth-infected African patient populations exposed to EBOV [55], we focused here on the effect of M2a polarization on rVSV/EBOV GP infection. While a large number of studies have used IL-4 and IL-13 to elicit the M2a phenotype in macrophages [31,56,57], we verified in our primary cells of interest, murine resident peritoneal macrophages (pmacs), that changes in gene expression occurred that were reflective of functional macrophage polarization following IL-4/-13 treatment.…”

Section: M2 Polarization Of Macrophages Increases Susceptibility To Rmentioning

confidence: 99%

IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection

et al. 2019

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BackgroundEbolavirus (EBOV) outbreaks, while sporadic, cause tremendous morbidity and mortality. No therapeutics or vaccines are currently licensed; however, a vaccine has shown promise in clinical trials. A critical step towards development of effective therapeutics is a better understanding of factors that govern host susceptibility to this pathogen. As macrophages are an important cell population targeted during virus replication, we explore the effect of cytokine polarization on macrophage infection.Methods/Main findingsWe utilized a BSL2 EBOV model virus, infectious, recombinant vesicular stomatitis virus encoding EBOV glycoprotein (GP) (rVSV/EBOV GP) in place of its native glycoprotein. Macrophages polarized towards a M2-like anti-inflammatory state by combined IL-4 and IL-13 treatment were more susceptible to rVSV/EBOV GP, but not to wild-type VSV (rVSV/G), suggesting that EBOV GP-dependent entry events were enhanced by these cytokines. Examination of RNA expression of known surface receptors that bind and internalize filoviruses demonstrated that IL-4/IL-13 stimulated expression of the C-type lectin receptor DC-SIGN in human macrophages and addition of the competitive inhibitor mannan abrogated IL-4/IL-13 enhanced infection. Two murine DC-SIGN-like family members, SIGNR3 and SIGNR5, were upregulated by IL-4/IL-13 in murine macrophages, but only SIGNR3 enhanced virus infection in a mannan-inhibited manner, suggesting that murine SIGNR3 plays a similar role to human DC-SIGN. In vivo IL-4/IL-13 administration significantly increased virus-mediated mortality in a mouse model and transfer of ex vivo IL-4/IL-13-treated murine peritoneal macrophages into the peritoneal cavity of mice enhanced pathogenesis.SignificanceThese studies highlight the ability of macrophage polarization to influence EBOV GP-dependent virus replication in vivo and ex vivo, with M2a polarization upregulating cell surface receptor expression and thereby enhancing virus replication. Our findings provide an increased understanding of the host factors in macrophages governing susceptibility to filoviruses and identify novel murine receptors mediating EBOV entry.

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Immunomodulation of COVID‐19 severity by helminth co‐infection: Implications for COVID‐19 vaccine efficacy

Akelew

Henok

Ebrahim

et al. 2021

Immunity Inflam & Disease

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), an emerging virus in late 2019 causing coronavirus disease 2019 (COVID‐19), has caused a catastrophic effect, resulting in an unprecedented global crisis. The immunopathology of COVID‐19 appears to be clearly associated with a dysregulated immune response leading to organ failure and death. Similarly, over two billion people worldwide are infected with helminth, with those living in low‐middle‐income countries disproportionately affected. Helminth infections have been shown to possess immunomodulatory effects in several conditions. Helminth co‐infection in COVID‐19 patients is one of the potential reasons for global attention to answer why COVID‐19 severity is still lower in helminth endemic countries. Recent studies have shown that helminth endemic countries showed fewer cases and deaths so far and helminth co‐infection might reduce the severity of COVID‐19. Moreover, lessons from other diseases with helminth co‐infection have been shown to substantially reduce vaccine efficacy that could also be implicated for COVID‐19. This immunomodulatory effect of helminth has intended and unintended consequences, both advantageous and disadvantageous which could decrease the severity of COVID‐19 and COVID‐19 vaccine efficacy respectively. Herewith, we discuss the overview of COVID‐19 immune response, immunomodulatory effects of helminth co‐infections in COVID‐19, lessons from other diseases, and perspectives on the efficacy of COVID‐19 vaccines.

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Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection

Cited by 80 publications

References 59 publications

Similar but different: virtual memory CD8 T cells as a memory‐like cell population

Similar but different: virtual memory CD8 T cells as a memory‐like cell population

IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection

Immunomodulation of COVID‐19 severity by helminth co‐infection: Implications for COVID‐19 vaccine efficacy

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