Neisseria Gonorrhoeae Lytic Transglycosylases LtgA and LtgD Reduce Host Innate Immune Signaling Through TLR2 and NOD2

Overview

Journal ACS Infect Dis

Specialties Infectious Diseases
Microbiology
Pharmacology

Date 2017 Jun 7

PMID 28585815

Citations 26

Authors

Kayla J Knilans

Kathleen T Hackett

James E Anderson

Chengyu Weng

Joseph P Dillard

Joseph A Duncan

Affiliations

Soon will be listed here.

Abstract

Neisseria gonorrhoeae releases anhydro peptidoglycan monomers during growth through the action of two lytic transglycosylases encoded in the N. gonorrhoeae genome, LtgA and LtgD. Because peptidoglycan and peptidoglycan components activate innate immune signaling, we hypothesized that the activity of LtgA and LtgD would influence the host responses to gonococcal infection. N. gonorrhoeae lacking LtgA and LtgD caused increased host production of inflammatory cytokines IL-1β and TNF-α. Culture supernatants from ΔltgA/ΔltgD N. gonorrhoeae contain more shed outer membrane-associated proteins and multimeric peptidoglycan fragments rather than monomers. These culture supernatants were more potent activators of host TLR2 and NOD2 signaling when compared to supernatants from the isogenic parental N. gonorrhoeae strain. Purified peptidoglycan monomers containing anhydro muramic acid produced by LtgA were poor stimulators of NOD2, whereas peptidoglycan monomers containing reducing muramic acid produced by host lysozyme were potent stimulators of NOD2. These data indicate that LtgA and LtgD reduce recognition of N. gonorrhoeae by TLR2 and NOD2.

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