AUTHOR=Silva Maike Paulino da , Silva Viviam de Oliveira , Pasetto Silvana , Ando-Suguimoto Ellen Sayuri , Kawamoto Dione , Mata Gardênia Márcia Silva Campos , Murata Ramiro Mendonça , Mayer Marcia Pinto Alves , Chen Casey 

TITLE=Aggregatibacter actinomycetemcomitans Outer Membrane Proteins 29 and 29 Paralogue Induce Evasion of Immune Response

JOURNAL=Frontiers in Oral Health

VOLUME=3

YEAR=2022

URL=https://www.frontiersin.org/journals/oral-health/articles/10.3389/froh.2022.835902

DOI=10.3389/froh.2022.835902

ISSN=2673-4842

ABSTRACT=<p><italic>Aggregatibacter actinomycetemcomitans</italic> (<italic>Aa</italic>) is abundant within the microbial dysbiotic community of some patients with periodontitis. <italic>Aa</italic> outer membrane protein 29 (OMP29), a member of the OMPA family, mediates the invasion of <italic>Aa</italic> to gingival epithelial cells (GECs). This study evaluated the effect of OMP29 and its paralogue OMP29<sup>par</sup> on the response of GECs to <italic>Aa</italic>. The <italic>omp29</italic> or/and <italic>omp29</italic><sup><italic>par</italic></sup> deletion mutants AaΔ29, AaΔ29P, and AaΔ29Δ29P were constructed, and recombinant <italic>Aa</italic> OMP29<sup>His</sup> was obtained. Microarray analysis and the evaluation of <italic>cxcl-8</italic> gene expression were performed to examine the response of GECs line OBA-09 to <italic>Aa</italic> and its mutants. The expression of <italic>cxcl-8</italic> and its product CXCL-8 was examined in LPS-stimulated OBA-09 cells with <italic>Aa</italic> OMP29<sup>His</sup>. Proteomics analysis showed that the deletion of <italic>omp29</italic> led to overexpression of both OMP29<sup>par</sup> and another membrane protein OMP39, the expression of which was further increased in AaΔ29Δ29P. OBA-09 cells challenged with AaΔ29Δ29P exhibited a higher expression of <italic>cxcl-8</italic> in comparison to wildtype <italic>Aa</italic> strain AaD7S or single-deletion mutants AaΔ29 or AaΔ29P. LPS-stimulated OBA-09 cells challenged with <italic>Aa</italic> OMP29<sup>His</sup> showed reduced expressions of <italic>cxcl-8</italic> and its product CXCL-8. OBA-09 cells challenged with AaΔ29Δ29P in comparison to <italic>Aa</italic> strain AaD7S resulted in higher expressions of genes involved in apoptosis and inflammatory response such as <italic>bcl2, birc3, casp3, c3, ep300, fas, fosb, grb2, il-1</italic>α<italic>, il-1</italic>β<italic>, il-6, cxcl-8, nr3c1, prkcq, socs3</italic>, and <italic>tnfrsf1</italic>β and reduced expressions of <italic>cd74, crp, faslg, tlr1</italic>, and <italic>vcam1</italic>. The results suggested a novel strategy of <italic>Aa</italic>, mediated by OMP29 and OMP29<sup>par</sup>, to evade host immune response by inhibiting CXCL-8 expression and modulating the genes involved in apoptosis and inflammatory response in GECs. Pending further confirmation, the strategy might interfere with the recruitment of neutrophils and dampen the host inflammatory response, leading to a more permissive subgingival niche for bacterial growth.</p>