Antibody Production in Murine Polymicrobial Sepsis-Kinetics and Key Players.

Oliver Nicolai,Julia Van Der Linde,Barbara M Bröker,Christian Pötschke,Katrin Schmoeckel,Murthy N Darisipudi,Dina Raafat

doi:10.3389/fimmu.2020.00828

Oliver Nicolai, Julia Van Der Linde + Show 5 more

Open Access

https://doi.org/10.3389/fimmu.2020.00828

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Abstract

Although antigen-specific priming of antibody responses is impaired during sepsis, there is nevertheless a strong increase in IgM and IgG serum concentrations. Using colon ascendens stent peritonitis (CASP), a mouse model of polymicrobial abdominal sepsis, we observed substantial increases in IgM as well as IgG of all subclasses, starting at day 3 and peaking 2 weeks after sepsis induction. The dominant source of antibody-secreting cells was by far the spleen, with a minor contribution of the mesenteric lymph nodes. Remarkably, sepsis induction in splenectomized mice did not change the dynamics of the serum IgM/IgG reaction, indicating that the marginal zone B cells, which almost exclusively reside in the spleen, are dispensable in such a setting. Hence, in systemic bacterial infection, the function of the spleen as dominant niche of antibody-producing cells can be compensated by extra-splenic B cell populations as well as other lymphoid organs. Depletion of CD4+ T cells did not affect the IgM response, while it impaired IgG generation of all subclasses with the exception of IgG3. Taken together, our data demonstrate that the robust class-switched antibody response in sepsis encompasses both T cell-dependent and -independent components.

Highlights

Sepsis is still associated with astoundingly high morbidity and mortality despite improvements in intensive care [1,2,3,4,5]
In colon ascendens stent peritonitis (CASP), the IgM-serum concentration increased from 111.5 ± 17.71 μg/mL (CI 95%: 92.9–130; untreated d1) to 710.2 ± 291.1 μg/mL (CI 95%: 349– 1,072) 14 days later (Figure 1A)
This increase was distributed among all IgG-subtypes (Figures 1C–F), indicating at least partially T cell-dependent processes

Summary

Introduction

Sepsis is still associated with astoundingly high morbidity and mortality despite improvements in intensive care [1,2,3,4,5]. Antigen presentation and T cell proliferation are impaired in the subsequent hypo-inflammatory phase, with a concomitant increase in concentrations of stress-induced anti-inflammatory glucocorticoids. These aforementioned effects, together with a Th2 cytokine bias, impair an effective immune response against primary or secondary infections [9,10,11,12,13,14,15,16]. This explains the fact that mortality from sepsis mostly occurs during this later phase [17, 18]

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