AUTHOR=Nahm Moon H. , Yu Jigui , Calix Juan J. , Ganaie Feroze 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.841062

DOI=10.3389/fimmu.2022.841062

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Streptococcus pneumoniae</italic> serotype 11A capsule polysaccharide dependent on the O-acetyltransferase gene <italic>wcjE</italic>. This triggers complement deposition and promotes opsonophagocytosis of encapsulated pneumococci. Even partial loss of ficolin-2 ligand expression through <italic>wcjE</italic> 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 <italic>wcjE</italic>-dependent epitopes co-isolated from single blood specimens, likely representing microevolutionary shifts towards <italic>wcjE</italic>-deficient populations during invasive pneumococcal disease (IPD). We find epidemiological evidence of <italic>wcjE</italic> 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.</p>