Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection

Justin Komguep Nono; Hlumani Ndlovu; Nada Abdel Aziz; Thabo Mpotje; Lerato Hlaka; Frank Brombacher

doi:10.1371/journal.pntd.0005675

Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection

PLoS Negl Trop Dis. 2017 Jun 26;11(6):e0005675. doi: 10.1371/journal.pntd.0005675. eCollection 2017 Jun.

Authors

Justin Komguep Nono^{1

2

3}, Hlumani Ndlovu^{1

2

4}, Nada Abdel Aziz^{1

2

5}, Thabo Mpotje^{1

2}, Lerato Hlaka^{1

2}, Frank Brombacher^{1

2}

Affiliations

¹ Cytokines and Diseases Group, International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town, South Africa.
² Division of Immunology, Health Science Faculty, University of Cape Town & Immunology of Infectious Disease Research Unit, South African Medical Research Council (SAMRC), Cape Town,South Africa.
³ The Medical Research Centre, Institute of Medical Research and Medicinal Plant Studies (IMPM), Ministry of Scientific Research and Innovation, Yaoundé, Cameroon.
⁴ Department of Integrative Biomedical Sciences, Health Sciences Faculty, University of Cape Town, Cape Town, South Africa.
⁵ Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.

Abstract

There is currently no vaccine against parasitic nematodes and the knowledge on the mechanisms by which protective immunity against this class of parasites is achieved is continuously expanding. Nematode parasites trigger a host protective type 2 immune response via interleukin-4 receptor alpha (IL-4Rα). Despite this central role, it is not known whether IL-4Rα has a role in maintaining host type 2 immune responses following polarization. To determine the role of IL-4Rα after polarization, we used a recently established strain of rosaCreERT2-/+IL-4Rα-/Lox mice where il4rα gene deletion can be temporally controlled. We show that sustained expression of IL-4Rα is required for the maintenance of type 2 immune responses and protective immunity following interruption after polarization with Nippostrongylus brasiliensis primary infection. Moreover, we show by temporal deletion of IL-4Rα prior to secondary infection with N. brasiliensis that signaling via this receptor drives more efficient recall of type 2 immune responses and clearance of the parasites. Together, this study demonstrates that sustained IL-4Rα mediated signaling is required for the maintenance of anti-nematode type 2 immune responses, describing a novel function for IL-4Rα that is distinct from its role in immune polarization.

MeSH terms

Animals
Disease Models, Animal
Gene Deletion
Interleukin-4 Receptor alpha Subunit / metabolism*
Mice
Mice, Knockout
Nippostrongylus / immunology*
Strongylida Infections / immunology*
Th2 Cells / immunology*

Substances

Interleukin-4 Receptor alpha Subunit

Grants and funding

This work was supported by the International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town. Further support was provided through the South African Medical Research Council (SAMRC) Unit on Immunology of Infectious Diseases (FB) and the South African Research Chair initiative (SARChi) to FB. JKN received a Sydney Brenner postdoctoral Fellowship from the Academy of Science of South Africa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.