IL-17A/IFN-γ producing γδ T cell functional dichotomy impacts cutaneous leishmaniasis in mice

Area of Science:

• Immunology
• Parasitology
• Dermatology

Background:

• γδ T cells are crucial immune cells with diverse functions.
• These cells can produce either IL-17A or IFN-γ, influencing immune responses.
• The specific roles of these γδ T cell subsets in cutaneous leishmaniasis remain unclear.

Purpose of the Study:

• To investigate the distinct roles of IL-17A- and IFN-γ-producing γδ T cells in cutaneous leishmaniasis.
• To determine the impact of γδ T cell functional dichotomy on disease pathogenesis and control.

Main Methods:

• Utilized mouse models of Leishmania amazonensis infection (Sv129, A129, C57BL/6).
• Analyzed γδ T cell populations and cytokine production (IL-17A, IFN-γ).
• Employed gene deficiency models (γδ T cell, IL-17 receptor) and adoptive cell transfer experiments.

Main Results:

• IL-17A-producing γδ T cells, particularly Vγ4+ cells, were identified as major producers in susceptible mice.
• Lipophosphoglycan from Leishmania amazonensis induced IL-17A production by γδ T cells.
• Mice lacking γδ T cells or IL-17 receptor showed reduced lesion size, confirming IL-17A's pathogenic role.
• Adoptive transfer of γδ T cells enhanced IFN-γ production and controlled lesion development.
• Transfer of IFN-γ-deficient γδ T cells abrogated disease control.

Conclusions:

• A functional dichotomy exists for γδ T cells in cutaneous leishmaniasis.
• IL-17A-producing γδ T cells contribute to disease pathogenesis.
• IFN-γ-producing γδ T cells demonstrate therapeutic potential for controlling leishmaniasis lesions.