Abstract
Complement is a critical system of enzymes, regulatory proteins, and receptors that regulates both innate and adaptive immune responses. Natural mutations in complement molecules highlight their requirement in regulation of a variety of human conditions including infectious disease and autoimmunity. As sentinels of the immune system, macrophages are specialized to respond to infectious microbes, as well as normal and altered self, and dictate appropriate immune responses. Complement components such as anaphylatoxins (C3a and C5a) and opsonins [C3b, C1q, mannan binding lectin (MBL)] influence macrophage responses. While anaphylatoxins C3a and C5a trigger inflammasome activation, opsonins such as C1q and related molecules (MBL and adiponectin) downregulate inflammasome activation and inflammation, and upregulate engulfment of apoptotic cells consistent with a pro-resolving or M2 macrophage phenotype. This review summarizes our current understanding of the influence of the complement system on macrophage polarization with an emphasis on C1q and related molecules.
Highlights
COMPLEMENT SYSTEM The complement system comprises over 35 cell associated and soluble molecules, which play a critical role in our innate immune response
We demonstrated that mouse bone marrow derived macrophages and peritoneal macrophages stimulated with C1q upregulated expression of engulfment machinery including Mer tyrosine kinase and the MerTK ligand Gas6, leading to development of a macrophage that is primed for efferocytosis [65]
CONCLUDING REMARKS The complement system has traditionally been considered an arm of the innate immune response required for promotion of inflammation and pathogen clearance
Summary
COMPLEMENT SYSTEM The complement system comprises over 35 cell associated and soluble molecules, which play a critical role in our innate immune response. Deficiency in early classical pathway component C1q is strongly associated with development of the autoimmune disease systemic lupus erythematosus (SLE), likely due to impaired opsonophagocytosis, and compromised removal of immune complexes and apoptotic cells [reviewed in Ref. While excessive or inappropriate complement activation is associated with almost all inflammatory or inflammation-related diseases including cancer, Alzheimer’s disease (AD), and metabolic disease [reviewed in Ref.
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