Related Experiment Video

Updated: May 7, 2026

Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses
10:10

Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses

Published on: November 16, 2016

12.5K

STAT1-L351F is associated with enhanced interferon signaling and susceptibility to Talaromyces marneffei infection

Yuchen Gu1,2, Haimei Zhang3, Qiaozi Lin4

  • 1Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China.

Frontiers in Immunology
|May 6, 2026
PubMed
Abstract

Insights

STAT1 gain-of-function (GOF) variants impair antifungal immunity, leading to increased susceptibility to Talaromyces marneffei infection. This study reveals how STAT1-L351F dysregulates immune responses, impacting fungal control.

Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Talaromyces marneffei causes disseminated infections, but the immune mechanisms involving STAT1 gain-of-function (GOF) variants are not fully understood.
  • STAT1 GOF variants, like L351F, are linked to increased susceptibility to fungal infections.

Purpose of the Study:

  • To investigate the immune alterations associated with the STAT1-L351F variant in a human pedigree and an in vivo model.
  • To elucidate the impact of STAT1-L351F on antifungal immunity against Talaromyces marneffei and other fungal pathogens.

Main Methods:

  • Human immunophenotyping, serum cytokine profiling, and ex vivo antifungal growth assays with patient peripheral blood mononuclear cells (PBMCs).
  • Mechanistic assays in HEK293T cells to assess STAT1 signaling.
  • In vivo studies using Stat1-L351F knock-in mice infected with T. marneffei, including transcriptomic analysis and JAK inhibition with ruxolitinib.

Main Results:

  • The proband exhibited an interferon-skewed cytokine profile and increased susceptibility of PBMCs to T. marneffei and Cryptococcus neoformans ex vivo.
  • STAT1-L351F demonstrated hyper-responsive interferon signaling.
  • Stat1-L351F mice showed increased lung fungal burden, severe pathology, altered immune cell frequencies (reduced NKT cells), and dysregulated immune programs.

Conclusions:

  • STAT1-L351F is associated with impaired antifungal control and selective permissiveness to fungal pathogens.
  • Dysregulated STAT1 signaling reshapes antifungal immunity, impacting IL-17-related immune programs.
  • This study provides a framework for understanding STAT1 GOF variants in fungal infections.
Keywords:
IL-17MDSCNKT cellsSTAT1 gain-of-functionTalaromyces marneffeiinterferonruxolitinibtalaromycosis

More Related Videos

Forward Genetics Screens Using Macrophages to Identify Toxoplasma gondii Genes Important for Resistance to IFN-γ-Dependent Cell Autonomous Immunity11:21

Forward Genetics Screens Using Macrophages to Identify Toxoplasma gondii Genes Important for Resistance to IFN-γ-Dependent Cell Autonomous Immunity

Published on: March 12, 2015

9.6K
High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes10:00

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes

Published on: March 24, 2015

13.6K

Related Concept Videos

Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
12.5K
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
73
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.2K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
13.7K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
10.3K