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LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner

Tian-Tian Liu1, Qing Yang1, Mi Li1

  • 1College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, State Key Laboratory of Virology, Wuhan University, Wuhan 430072, China; and.

Journal of Immunology (Baltimore, Md. : 1950)
|May 17, 2016
PubMed

Insights

The protein LSm14A is crucial for inducing antiviral cytokines in dendritic cells (DCs) in vivo. Its deficiency impairs antiviral responses by affecting MITA/STING levels and mRNA processing in DCs.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Viral infections activate innate immune responses through antiviral cytokines.
  • The protein LSm14A's role in antiviral cytokine induction was previously shown in cell lines, but in vivo data was missing.

Purpose of the Study:

  • To investigate the in vivo function of LSm14A in antiviral immune responses.
  • To elucidate the mechanism by which LSm14A regulates antiviral cytokine induction.

Main Methods:

  • Generation of LSm14A-deficient (Lsm14a(-/-)) mice.
  • Analysis of antiviral cytokine induction in dendritic cells (DCs), macrophages, and fibroblasts from Lsm14a(-/-) mice.
  • Assessment of viral infection models (HSV-1, MHV-68, VSV, Sendai virus).
  • Evaluation of MITA/STING protein levels and mRNA precursor processing.

Main Results:

  • LSm14A deficiency specifically impaired antiviral cytokine induction in DCs, but not in macrophages or fibroblasts.
  • Impaired cytokine induction in Lsm14a(-/-) DCs was observed for DNA viruses (HSV-1, MHV-68) and some RNA viruses (VSV), but not Sendai virus.
  • LSm14A deficiency led to downregulated MITA/STING levels in DCs due to impaired nuclear mRNA precursor processing.
  • This resulted in compromised innate and adaptive antiviral immune responses.

Conclusions:

  • LSm14A plays a critical, cell-specific role in antiviral immunity, particularly in dendritic cells.
  • LSm14A regulates antiviral responses by controlling MITA/STING levels via nuclear mRNA precursor processing.
  • These findings reveal a novel mechanism for regulating antiviral immunity at the level of mRNA processing in a cell-specific manner.

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