Abstract
Recent advances in complement research have revolutionized our understanding of its role in immune responses. The immunomodulatory features of complement in infections by intracellular pathogens, e.g., viruses, are attracting increasing attention. Thereby, local production and activation of complement by myeloid-derived cells seem to be crucial. We could recently show that C3, a key player of the complement cascade, is required for effective defense against the intracellular bacterium Chlamydia psittaci. Avian zoonotic strains of this pathogen cause life-threatening pneumonia with systemic spread in humans; closely related non-avian strains are responsible for less severe diseases of domestic animals with economic loss. To clarify how far myeloid- and non-myeloid cell-derived complement contributes to immune response and resulting protection against C. psittaci, adoptive bone marrow transfer experiments focusing on C3 were combined with challenge experiments using a non-avian (BSL 2) strain of this intracellular bacterium. Surprisingly, our data prove that for C. psittaci-induced pneumonia in mice, non-myeloid-derived, circulating/systemic C3 has a leading role in protection, in particular on the development of pathogen-specific T- and B- cell responses. In contrast, myeloid-derived and most likely locally produced C3 plays only a minor, mainly fine-tuning role. The work we present here describes authentic, although less pronounced, antigen directed immune responses.
Highlights
Complement is an essential part of the immune system
In order to elucidate the contribution of myeloid and nonmyeloid-derived complement in defense against intracellular chlamydiae, C57BL/6J WT (C3+/+) and complement factor 3 (C3)−/− mice were irradiated and adoptive Bone Marrow (BM) transfer was performed to generate chimeric mice for C.ps. challenge experiments (Figure 1A)
From that one can draw the conclusion that approx. ≥95% of the circulating C3 in WT WT BM chimeric mice during steady state and during C.ps. infection is derived from non-myeloid cells, most likely, primarily of the liver— and up to 5% might be produced and secreted by nonmyeloid cells
Summary
Complement is an essential part of the immune system. It consists of more than 50 fluid-phase and membrane-bound proteins: zymogens, mediators, regulators, and receptors. It plays a vital role in the defense against invading microorganisms. Complement is early activated in infection and functionally placed on the crossroads of innate and adaptive immunity [1]. Complement factors are mainly provided by hepatocytes, but they are produced in epithelial, endothelial, and adipose tissue and other cell types [1, 2]. Local production of complement proteins by immune
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