Microbial Evasion of IgA Functions

During coevolution with their respective hosts, microorganisms have developed strategies to circumvent host innate and adaptive immune factors, including those that operate at mucosal surfaces. One such factor is the IgA1 protease produced by the three principal causes of bacterial meningitis in humans, Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae; by phylogenetically closely related species; and by certain bacteria implicated in infections of the urinary tract and periodontium. The functionally identical postproline endopeptidases evolved along five distinct evolutionary lineages and cleave one specific peptide bond adjacent to a carbohydrate side chain in the elongated hinge region of IgA1. Cleavage results in the release of monomeric, still antigen-binding Fab fragments and allows the bacteria to interfere with all protective functions of IgA1 antibodies and, in addition, to take advantage of released Fab fragments for coating of surface epitopes and for increasing the hydrophobic properties of encapsulated bacteria. Other immune escape mechanisms include expression of IgA-binding proteins and glycosidic attack of the functionally important carbohydrate moiety of SIgA.