Polymicrobial Sepsis Chronic Immunoparalysis Is Defined by Diminished Ag-Specific T Cell-Dependent B Cell Responses

Area of Science:

• Immunology
• Infectious Disease
• Cellular Biology

Background:

• Sepsis causes immunosuppression, impairing host defense against infections.
• CD4 T cells and B cells are crucial for adaptive immunity but are functionally impaired during sepsis.
• The impact of sepsis on CD4 T cell-dependent B cell responses, particularly T follicular helper (Tfh) cell interactions, remains poorly understood.

Purpose of the Study:

• To investigate how sepsis affects CD4 T cell-dependent B cell responses.
• To elucidate the mechanisms by which sepsis-induced immunosuppression impacts humoral immunity.
• To define the role of sepsis in altering Tfh cell differentiation and function.

Main Methods:

• Utilized the cecal ligation and puncture (CLP) mouse model to induce sepsis.
• Assessed antibody production following challenge with influenza A virus or TNP-KLH.
• Immunized mice with a model antigen (2W1S-PE) to track antigen-specific CD4 T cells and B cells.

Main Results:

• Reduced antibody production was observed in septic mice early and late after CLP surgery.
• Sepsis blunted the differentiation and class switching of antigen-specific B cells.
• Septic mice exhibited reduced expansion of antigen-specific CD4 T cells and impaired Tfh cell differentiation.

Conclusions:

• Cecal ligation and puncture-induced sepsis significantly impairs humoral immunity.
• Sepsis affects both the number and function of antigen-specific B cells and CD4 Tfh cells.
• These findings define a period of chronic immunoparalysis following sepsis, impacting adaptive immune responses.