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Amebiasis01:28

Amebiasis

Entamoeba histolytica, a protozoan parasite, is responsible for intestinal and extraintestinal amebiasis. Though a significant proportion of infections remain asymptomatic, approximately 50 million individuals annually are estimated to present with clinical disease, resulting in up to 100,000 deaths globally. The disease burden is disproportionately high in regions with lower socioeconomic status, such as parts of India, Africa, Mexico, and Latin America.Etiology and TransmissionThe infective...

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PD-L2 Inhibits Protective Immunity, Th2 Cell Functional Quality, and GATA-3 Expression During Filarial Nematode

Johanna A Knipper1,2, Sharon M Campbell1, Judith E Allen1,3

  • 1Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK.

European Journal of Immunology
|August 4, 2025
PubMed
Summary

Programmed death-ligand 2 (PD-L2) inhibits protective immunity against filarial nematodes by impairing T helper 2 (Th2) cell function. Blocking PD-L2 enhances resistance and maintains Th2 cell quality during infection.

Keywords:
B cellHelminthT cellTh2immune‐regulation

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Area of Science:

  • Immunology
  • Parasitology
  • Molecular Biology

Background:

  • Filarial nematodes affect over 200 million people, causing immune suppression that delays protective immunity.
  • Immune suppression during filariasis predominantly involves a Type 2 immune response, often leading to T helper 2 (Th2) cell hypo-responsiveness.
  • Previous research indicated that PD-1 co-inhibition impairs Th2 cell function, hindering protective immunity.

Purpose of the Study:

  • To investigate the role of PD-L2 in Th2 cell hypo-responsiveness and protective immunity during filarial infection.
  • To determine the impact of PD-L2 on GATA-3 expression in CD4+ T cells.
  • To elucidate the contribution of B cells expressing PD-L2 to immune suppression in filariasis.

Main Methods:

  • Utilized the murine model Litomosoides sigmodontis for filarial infection.
  • Employed wild-type (WT), PD-L2 knockout (PD-L2-/-), and B cell-deficient (Jh-/-) mice.
  • Conducted bone marrow chimaera experiments to assess cell-specific roles of PD-L2.

Main Results:

  • PD-L2 deficiency in mice correlated with increased resistance to L. sigmodontis and improved Th2 cell functional quality.
  • Loss of GATA-3 expression in CD4+ T cells was linked to Th2 cell hypo-responsiveness in WT mice, but not in PD-L2-/- mice.
  • While B cells express PD-L2 and play a suppressive role, they do not instigate Th2 cell hypo-responsiveness, and their PD-L2 expression is not critical for resistance.

Conclusions:

  • PD-L2 actively inhibits protective immunity against L. sigmodontis by downregulating GATA-3 and inducing Th2 cell-intrinsic hypo-responsiveness.
  • B cells contribute to immune suppression independently of PD-L2 and do not drive Th2 cell hypo-responsiveness.
  • Targeting PD-L2 may represent a therapeutic strategy to enhance immunity against filarial nematode infections.