IL-4 mediated resistance of BALB/c mice to visceral leishmaniasis is independent of IL-4Rα signaling via T cells

Emma McFarlane, Thabang Mokgethi, Paul M. Kaye, Ramona Hurdayal, Frank Brombacher, James Alexander, Katharine C. Carter

Research output: Contribution to journalArticle

Abstract

Previous studies infecting global IL-4Rα −/−, IL-4 −/−, and IL-13 −/− mice on a BALB/c background with the visceralizing parasite Leishmania donovani have shown that the T helper 2 cytokines, IL-4, and IL-13, play influential but not completely overlapping roles in controlling primary infection. Subsequently, using macrophage/neutrophil-specific IL-4Rα deficient BALB/c mice, we demonstrated that macrophage/neutrophil unresponsiveness to IL-4 and IL-13 did not have a detrimental effect during L. donovani infection. Here we expand on these findings and show that CD4 + T cell-(Lck cre), as well as pan T cell-(iLck cre) specific IL-4Rα deficient mice, on a BALB/c background, unlike global IL-4Rα deficient mice, are also not adversely affected in terms of resistance to primary infection with L. donovani. Our analysis suggested only a transient and tissue specific impact on disease course due to lack of IL-4Rα on T cells, limited to a reduced hepatic parasite burden at day 30 post-infection. Consequently, the protective role(s) demonstrated for IL-4 and IL-13 during L. donovani infection are mediated by IL-4Rα-responsive cell(s) other than macrophages, neutrophils and T cells.

LanguageEnglish
Article number1957
Number of pages13
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 16 Aug 2019

Fingerprint

Visceral Leishmaniasis
Leishmania donovani
Interleukin-4
Interleukin-13
T-Lymphocytes
Infection
Neutrophils
Macrophages
Parasites
Cytokines
Liver

Keywords

  • Leishmania donovani
  • IL-4Rα
  • IL-4
  • t-cells
  • mice

Cite this

@article{c1655dec1d6948b9ad1f83f0fecfd333,
title = "IL-4 mediated resistance of BALB/c mice to visceral leishmaniasis is independent of IL-4Rα signaling via T cells",
abstract = "Previous studies infecting global IL-4Rα −/−, IL-4 −/−, and IL-13 −/− mice on a BALB/c background with the visceralizing parasite Leishmania donovani have shown that the T helper 2 cytokines, IL-4, and IL-13, play influential but not completely overlapping roles in controlling primary infection. Subsequently, using macrophage/neutrophil-specific IL-4Rα deficient BALB/c mice, we demonstrated that macrophage/neutrophil unresponsiveness to IL-4 and IL-13 did not have a detrimental effect during L. donovani infection. Here we expand on these findings and show that CD4 + T cell-(Lck cre), as well as pan T cell-(iLck cre) specific IL-4Rα deficient mice, on a BALB/c background, unlike global IL-4Rα deficient mice, are also not adversely affected in terms of resistance to primary infection with L. donovani. Our analysis suggested only a transient and tissue specific impact on disease course due to lack of IL-4Rα on T cells, limited to a reduced hepatic parasite burden at day 30 post-infection. Consequently, the protective role(s) demonstrated for IL-4 and IL-13 during L. donovani infection are mediated by IL-4Rα-responsive cell(s) other than macrophages, neutrophils and T cells.",
keywords = "Leishmania donovani, IL-4Rα, IL-4, t-cells, mice",
author = "Emma McFarlane and Thabang Mokgethi and Kaye, {Paul M.} and Ramona Hurdayal and Frank Brombacher and James Alexander and Carter, {Katharine C.}",
year = "2019",
month = "8",
day = "16",
doi = "10.3389/fimmu.2019.01957",
language = "English",
volume = "10",
journal = "Frontiers in Immunology",
issn = "1664-3224",

}

IL-4 mediated resistance of BALB/c mice to visceral leishmaniasis is independent of IL-4Rα signaling via T cells. / McFarlane, Emma; Mokgethi, Thabang; Kaye, Paul M.; Hurdayal, Ramona; Brombacher, Frank; Alexander, James; Carter, Katharine C.

In: Frontiers in Immunology, Vol. 10, 1957, 16.08.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - IL-4 mediated resistance of BALB/c mice to visceral leishmaniasis is independent of IL-4Rα signaling via T cells

AU - McFarlane, Emma

AU - Mokgethi, Thabang

AU - Kaye, Paul M.

AU - Hurdayal, Ramona

AU - Brombacher, Frank

AU - Alexander, James

AU - Carter, Katharine C.

PY - 2019/8/16

Y1 - 2019/8/16

N2 - Previous studies infecting global IL-4Rα −/−, IL-4 −/−, and IL-13 −/− mice on a BALB/c background with the visceralizing parasite Leishmania donovani have shown that the T helper 2 cytokines, IL-4, and IL-13, play influential but not completely overlapping roles in controlling primary infection. Subsequently, using macrophage/neutrophil-specific IL-4Rα deficient BALB/c mice, we demonstrated that macrophage/neutrophil unresponsiveness to IL-4 and IL-13 did not have a detrimental effect during L. donovani infection. Here we expand on these findings and show that CD4 + T cell-(Lck cre), as well as pan T cell-(iLck cre) specific IL-4Rα deficient mice, on a BALB/c background, unlike global IL-4Rα deficient mice, are also not adversely affected in terms of resistance to primary infection with L. donovani. Our analysis suggested only a transient and tissue specific impact on disease course due to lack of IL-4Rα on T cells, limited to a reduced hepatic parasite burden at day 30 post-infection. Consequently, the protective role(s) demonstrated for IL-4 and IL-13 during L. donovani infection are mediated by IL-4Rα-responsive cell(s) other than macrophages, neutrophils and T cells.

AB - Previous studies infecting global IL-4Rα −/−, IL-4 −/−, and IL-13 −/− mice on a BALB/c background with the visceralizing parasite Leishmania donovani have shown that the T helper 2 cytokines, IL-4, and IL-13, play influential but not completely overlapping roles in controlling primary infection. Subsequently, using macrophage/neutrophil-specific IL-4Rα deficient BALB/c mice, we demonstrated that macrophage/neutrophil unresponsiveness to IL-4 and IL-13 did not have a detrimental effect during L. donovani infection. Here we expand on these findings and show that CD4 + T cell-(Lck cre), as well as pan T cell-(iLck cre) specific IL-4Rα deficient mice, on a BALB/c background, unlike global IL-4Rα deficient mice, are also not adversely affected in terms of resistance to primary infection with L. donovani. Our analysis suggested only a transient and tissue specific impact on disease course due to lack of IL-4Rα on T cells, limited to a reduced hepatic parasite burden at day 30 post-infection. Consequently, the protective role(s) demonstrated for IL-4 and IL-13 during L. donovani infection are mediated by IL-4Rα-responsive cell(s) other than macrophages, neutrophils and T cells.

KW - Leishmania donovani

KW - IL-4Rα

KW - IL-4

KW - t-cells

KW - mice

UR - https://www.frontiersin.org/journals/immunology

U2 - 10.3389/fimmu.2019.01957

DO - 10.3389/fimmu.2019.01957

M3 - Article

VL - 10

JO - Frontiers in Immunology

T2 - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1957

ER -