Acute IL-4 Governs Pathogenic T Cell Responses during Leishmania major Infection

Barun Poudel; Matthew S Yorek; Lalita Mazgaeen; Scott A Brown; Thirumala-Devi Kanneganti; Prajwal Gurung

doi:10.4049/immunohorizons.2000076

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Acute IL-4 Governs Pathogenic T Cell Responses during Leishmania major Infection

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Acute IL-4 Governs Pathogenic T Cell Responses during Leishmania major Infection

Barun Poudel, Matthew S Yorek, Lalita Mazgaeen, Scott A Brown, Thirumala-Devi Kanneganti and Prajwal Gurung

ImmunoHorizons, Vol.4(9), pp.546-560

09/18/2020

DOI: 10.4049/immunohorizons.2000076

PMCID: PMC7640617

PMID: 32948646

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Abstract

spp. infection is a global health problem affecting more than 2 million people every year with 300 million at risk worldwide. It is well established that a dominant Th1 response (IFN-γ, a hallmark Th1 cytokine) provides resistance, whereas a dominant Th2 response (IL-4, a hallmark Th2 cytokine) confers susceptibility during infection. Given the important role of IL-4 during infection, we used IL-4-neutralizing Abs to investigate the cellular and molecular events regulated by IL-4 signaling. As previously published, neutralization of IL-4 in -infected BALB/c mice (a susceptible strain) provided protection when compared with control -infected BALB/c mice. Despite this protection, IFN-γ production by T cells was dramatically reduced. Temporal neutralization of IL-4 revealed that acute IL-4 produced within the first days of infection is critical for not only programming IL-4-producing Th2 CD4 T cells, but for promoting IFN-γ produced by CD8 T cells. Mechanistically, IL-4 signaling enhances anti-CD3-induced Tbet and IFN-γ expression in both CD4 and CD8 T cells. Given the pathogenic role of IFN-γ-producing CD8 T cells, our data suggest that IL-4 promotes cutaneous leishmaniasis pathology by not only promoting Th2 immune responses but also pathogenic CD8 T cell responses. Our studies open new research grounds to investigate the unsuspected role of IL-4 in regulating both Th1 and Th2 responses.

Details

Title: Subtitle: Acute IL-4 Governs Pathogenic T Cell Responses during Leishmania major Infection
Creators: Barun Poudel - University of Iowa
Matthew S Yorek - University of Iowa
Lalita Mazgaeen - University of Iowa
Scott A Brown - St. Jude Children's Research Hospital
Thirumala-Devi Kanneganti - St. Jude Children's Research Hospital
Prajwal Gurung - University of Iowa
Resource Type: Journal article
Publication Details: ImmunoHorizons, Vol.4(9), pp.546-560
DOI: 10.4049/immunohorizons.2000076
PMID: 32948646
PMCID: PMC7640617
NLM abbreviation: Immunohorizons
ISSN: 2573-7732
eISSN: 2573-7732
Grant note: R01 AI101935 / NIAID NIH HHS R01 AR056296 / NIAMS NIH HHS R37 AI101935 / NIAID NIH HHS R21 AI148904 / NIAID NIH HHS R01 CA163507 / NCI NIH HHS R01 AI124346 / NIAID NIH HHS
Language: English
Date published: 09/18/2020
Academic Unit: Infectious Diseases; Stead Family Department of Pediatrics; Pathology; Internal Medicine
Record Identifier: 9984360046002771

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