Ficolin-2 Lectin Complement Pathway Mediates Capsule-Specific Innate Immunity Against Invasive Pneumococcal Disease

Frontiers in Immunology

Juan J. Calix¹  Jigui Yu²  Feroze Ganaie²  Moon H. Nahm² 

[1] Division of Infectious Diseases, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States;Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States;

关键词: lectin complement pathway;    ficolin-2;    Streptococcus pneumoniae;    innate immunity;    capsule;   

DOI  :  10.3389/fimmu.2022.841062

来源: DOAJ

【 摘 要 】

Reports conflict regarding which lectin-microbial ligand interactions elicit a protective response from the lectin pathway (LP) of complement. Using fluorescent microscopy, we demonstrate the human lectin ficolin-2 binds to Streptococcus pneumoniae serotype 11A capsule polysaccharide dependent on the O-acetyltransferase gene wcjE. This triggers complement deposition and promotes opsonophagocytosis of encapsulated pneumococci. Even partial loss of ficolin-2 ligand expression through wcjE mutation abrogated bacterial killing. Ficolin-2 did not interact with any pneumococcal non-capsule structures, including teichoic acid. We describe multiple 11A clonal derivatives expressing varying degrees of wcjE-dependent epitopes co-isolated from single blood specimens, likely representing microevolutionary shifts towards wcjE-deficient populations during invasive pneumococcal disease (IPD). We find epidemiological evidence of wcjE impairing pneumococcal invasiveness, supporting that the LP’s ficolin-2 axis provides innate, serotype-specific serological protection against IPD. The fact that the LP is triggered by only a few discrete carbohydrate ligands emphasizes the need to reevaluate its impact in a glycopolymer-specific manner.

【 授权许可】

Unknown