Gut Microbial Membership Modulates CD4 T Cell Reconstitution and Function after Sepsis

Area of Science:

• Immunology
• Microbiome research
• Infectious disease

Background:

• Sepsis causes transient lymphopenia and alters CD4 T cells in survivors.
• Previous work showed lymphopenia-induced proliferation aids CD4 T cell recovery.
• The role of gut microbiome leakage in CD4 T cell responses during sepsis is unclear.

Purpose of the Study:

• To investigate the impact of gut microbiome leakage on CD4 T cells during polymicrobial sepsis.
• To explore the number and function of CD4 T cells specific for segmented filamentous bacterium (SFB) after cecal ligation and puncture (CLP)-induced sepsis.

Main Methods:

• Used mice with or without SFB, subjected to CLP-induced sepsis.
• Analyzed endogenous CD4 T cells specific for SFB.
• Assessed resistance to secondary Listeria infection.

Main Results:

• SFB-specific CD4 T cells proliferated in CLP-treated mice harboring SFB, but not in those without SFB.
• Mice treated with CLP and SFB showed resistance to secondary infection with SFB Ag-expressing Listeria.
• This suggests sepsis primes SFB-specific CD4 T cells for a protective response.

Conclusions:

• Ag-driven proliferation of SFB-specific CD4 T cells contributes to numerical recovery in sepsis survivors.
• Intestinal barrier health, influenced by specific gut bacteria, modulates CD4 T cell responses post-sepsis.
• These findings highlight the microbiome's role in adaptive immunity following sepsis.