Herpes simplex virus type 1 impairs mucosal-associated invariant T cells

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes crucial for immunity against microbial pathogens.
• Herpes simplex virus type 1 (HSV-1) is a common virus known for manipulating host immune responses.
• The interaction between HSV-1 and MAIT cells remains poorly understood, particularly whether HSV-1 can infect and modulate MAIT cell functions.

Purpose of the Study:

• To investigate whether HSV-1 can infect human MAIT cells.
• To determine the impact of HSV-1 infection on MAIT cell functionality.
• To explore the mechanisms by which HSV-1 may affect MAIT cell responses.

Main Methods:

• Infection of primary human MAIT cells (including CD4±/CD8± and CD56± subpopulations) with HSV-1.
• Assessment of MAIT cell responses to T cell receptor (TCR)-dependent stimulation and cytokine stimulation (IL-12/IL-18).
• Analysis of MAIT cell cytotoxic potential, effector cytokine synthesis, and cytokine receptor expression.
• Evaluation of MAIT cells exposed to HSV-1-infected fibroblasts.

Main Results:

• HSV-1 successfully infects primary human MAIT cells across different subpopulations.
• HSV-1 infection significantly inhibits MAIT cell functional capacity, including responses to TCR and cytokine stimulation.
• Infected MAIT cells exhibit reduced cytotoxicity, diminished effector cytokine production, and decreased IL-18R expression.
• MAIT cells exposed to HSV-1-infected fibroblasts, even without direct infection, show suppressed effector responses.

Conclusions:

• HSV-1 can directly infect human MAIT cells, leading to profound functional impairment.
• Exposure to HSV-1-infected cells suppresses MAIT cell function, suggesting a broader immunomodulatory role for HSV-1.
• This study identifies a novel mechanism of immune evasion by HSV-1 through the manipulation of MAIT cells.