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Nitric oxide detoxification systems enhance survival of Neisseria meningitidis in human macrophages and in nasopharyngeal mucosa

Nitric oxide detoxification systems enhance survival of Neisseria meningitidis in human macrophages and in nasopharyngeal mucosa
Nitric oxide detoxification systems enhance survival of Neisseria meningitidis in human macrophages and in nasopharyngeal mucosa

Nitric oxide (NO) contributes to mammalian host defense by direct microbicidal activity and as a signaling molecule of innate immune responses. Macrophages produce NO via the inducible NO synthase (iNOS). The genome of Neisseria meningitidis includes two genes, norB (encoding nitric oxide reductase) and cycP (encoding cytochrome c'), both of which detoxify NO in pure cultures of N. meningitidis. We show here that norB, and to a lesser extent cycP, enhance survival of N. meningitidis within primary human macrophages. Furthermore, accumulation of lysosome-associated membrane protein 1 (LAMP-1) is modified in phagosomes containing an isogenic norB mutant of N. meningitidis compared to the wild type. The survival enhancement conferred by norB and cycP is ablated by pretreatment of macrophages with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Despite this evidence that NO detoxification confers advantage, we find, using a highly sensitive chemiluminescence technique, that human macrophage-associated [NO] is low even after activation by lipopolysaccharide and interferon alpha. Furthermore, wild-type N. meningitidis further depletes cell-associated NO during phagocytosis by an active mechanism and survives relatively poorly in the presence of L-NMMA, suggesting that the wild-type organism may utilize NO for optimal survival during intracellular life. The natural habitat of N. meningitidis is the human nasopharynx. Using a nasopharyngeal mucosa organ culture system, we show that mutants lacking norB and cycP also survive poorly in nasopharyngeal tissue compared to wild-type N. meningitidis. These findings indicate that the meningococcus requires active NO detoxification systems for optimal survival during experimental nasopharyngeal colonization and processing by human phagocytic cells.

Cells, Cultured, Humans, Lysosome-Associated Membrane Glycoproteins, Macrophages, Membrane Glycoproteins, Mucous Membrane, Nasopharynx, Neisseria meningitidis, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Phagocytosis, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
0019-9567
3322-3329
Stevanin, Tânia M.
ff5fc52c-a001-42d6-9b01-3cb24e4758b1
Moir, James W.B.
f6831b5f-5cfd-4c56-b3cd-6782f413a07f
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Stevanin, Tânia M.
ff5fc52c-a001-42d6-9b01-3cb24e4758b1
Moir, James W.B.
f6831b5f-5cfd-4c56-b3cd-6782f413a07f
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Stevanin, Tânia M., Moir, James W.B. and Read, Robert C. (2005) Nitric oxide detoxification systems enhance survival of Neisseria meningitidis in human macrophages and in nasopharyngeal mucosa. Infection and Immunity, 73 (6), 3322-3329. (doi:10.1128/IAI.73.6.3322-3329.2005).

Record type: Article

Abstract

Nitric oxide (NO) contributes to mammalian host defense by direct microbicidal activity and as a signaling molecule of innate immune responses. Macrophages produce NO via the inducible NO synthase (iNOS). The genome of Neisseria meningitidis includes two genes, norB (encoding nitric oxide reductase) and cycP (encoding cytochrome c'), both of which detoxify NO in pure cultures of N. meningitidis. We show here that norB, and to a lesser extent cycP, enhance survival of N. meningitidis within primary human macrophages. Furthermore, accumulation of lysosome-associated membrane protein 1 (LAMP-1) is modified in phagosomes containing an isogenic norB mutant of N. meningitidis compared to the wild type. The survival enhancement conferred by norB and cycP is ablated by pretreatment of macrophages with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Despite this evidence that NO detoxification confers advantage, we find, using a highly sensitive chemiluminescence technique, that human macrophage-associated [NO] is low even after activation by lipopolysaccharide and interferon alpha. Furthermore, wild-type N. meningitidis further depletes cell-associated NO during phagocytosis by an active mechanism and survives relatively poorly in the presence of L-NMMA, suggesting that the wild-type organism may utilize NO for optimal survival during intracellular life. The natural habitat of N. meningitidis is the human nasopharynx. Using a nasopharyngeal mucosa organ culture system, we show that mutants lacking norB and cycP also survive poorly in nasopharyngeal tissue compared to wild-type N. meningitidis. These findings indicate that the meningococcus requires active NO detoxification systems for optimal survival during experimental nasopharyngeal colonization and processing by human phagocytic cells.

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More information

Published date: June 2005
Keywords: Cells, Cultured, Humans, Lysosome-Associated Membrane Glycoproteins, Macrophages, Membrane Glycoproteins, Mucous Membrane, Nasopharynx, Neisseria meningitidis, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Phagocytosis, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.

Identifiers

Local EPrints ID: 416378
URI: http://eprints.soton.ac.uk/id/eprint/416378
ISSN: 0019-9567
PURE UUID: fe18dfd7-e241-409b-8142-32aca66b6acd
ORCID for Robert C. Read: ORCID iD orcid.org/0000-0002-4297-6728

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Date deposited: 14 Dec 2017 17:30
Last modified: 10 Nov 2021 03:30

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Contributors

Author: Tânia M. Stevanin
Author: James W.B. Moir
Author: Robert C. Read ORCID iD

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