Figure 3

Model for the role of FcαRI in mucosal immunity. In humans, immunoglobulin A (IgA) is expressed in three different forms. (a) In homeostatic conditions dimeric IgA (dIgA) functions as intermediary molecule that is secreted as SIgA, which inhibits bacterial invasion. Monomeric serum IgA functions as anti-inflammatory molecule through targeting FcαRI–inhibitory capacity through FcR γ-chain ITAM (ITAMi) signaling. (b) When microorganisms have been able to breach the epithelial barrier, dIgA can opsonize these pathogens. Recruited neutrophils that express FcαRI will clear the infection through phagocytosis and release of leukotrien B4 (LTB4, via active immunoreceptor tyrosine-based activation motif (ITAM) signaling), which may lead to a self-controlled positive feedback loop, until pathogens have been eliminated. Hence, in case of local bacterial translocation, dIgA represents a proinflammatory molecule and functions as the second line of innate mucosal immune defense. (c) Finally, pathogens that have entered the portal circulation are opsonized by serum IgA, and subsequently phagocytosed by FcαRI-positive Kupffer cells. As such, serum IgA can function as proinflammatory antibody when systemic bacterial translocation occurs, and interaction with FcαRI on Kupffer cells represent a third line of defence at the interface of mucosal and systemic immunity. Green, non- or anti-inflammatory and red, proinflammatory.

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