Abstract

Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP) 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool’s development, which is not complete 8 weeks after secondary immunization.

Highlights

  • Sepsis is still associated with astoundingly high morbidity and mortality despite improvements in intensive care [1,2]

  • Mice were anaesthetized with ketamine/ xylazine (100 mg/10 mg per kg bodyweight) and an 18 G stent was implanted into their colon ascendens

  • Experimental mouse model of humoral memory We established an experimental mouse model of humoral memory against which to measure the effects of sepsis

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Summary

Introduction

Sepsis is still associated with astoundingly high morbidity and mortality despite improvements in intensive care [1,2]. If sepsis changes the composition of supporting cell types in the survival niche, long-lived plasma cell populations could be affected and humoral memory could thereby be weakened. This is how sepsis would dampen the protection provided by vaccination, or in general, the adaptive protection against pathogens [3536.-37], resulting in susceptibility to further infections. Memory B cells maintain protective serum antibody concentrations because they are activated via their TLRs by the numerous microbial components that flood the system during sepsis [38,39] To test these hypotheses, we have established immune memory in mice by vaccinating and boosting with a defined antigen. We found that sepsis reduced antigen-specific serum IgG as well as the number of antigen-specific antibody secreting cells in the bone marrow

Materials and Methods
Results and Discussion
21 Suppl 2
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