Abstract
Macrophages produce nitric oxide (NO) via the inducible nitric oxide synthase as part of a successful response to infection. The gene norB of Neisseria meningitidis encodes a NO reductase which enables utilization and consumption of NO during microaerobic respiration and confers resistance to nitrosative stress-related killing by human monocyte-derived macrophages (MDM). In this study we confirmed that NO regulates cytokine and chemokine release by resting MDM: accumulation of TNF-alpha, IL-12, IL-10, CCL5 (RANTES) and CXCL8 (IL-8) in MDM supernatants was significantly modified by the NO-donor S-nitroso-N-penicillamine (SNAP). Using a protein array, infection of MDM with N. meningitidis was shown to be associated with secretion of a wide range of cytokines and chemokines. To test whether NO metabolism by N. meningitidis modifies release of NO-regulated cytokines, we infected MDM with wild-type organisms and an isogenic norB strain. Resulting expression of the cytokines TNF-alpha and IL-12, and the chemokine CXCL8 was increased and production of the cytokine IL-10 and the chemokine CCL5 was decreased in noi-B-infected MDM, in comparison to wild-type. Addition of SNAP to cultures infected with wild-type mimicked the effect observed in cultures infected with the norB mutant. In Conclusion, Not-B-catalysed removal of NO modifies cellular release of NO-regulated cytokines and chemokines. (c) 2007 Elsevier Masson SAS. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 981-987 |
| Number of pages | 7 |
| Journal | Microbes and infection |
| Volume | 9 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Jul 2007 |
Keywords
- Neisseria meningitidis
- nitric oxides
- cytokines
- NECROSIS-FACTOR-ALPHA
- OXIDATIVE STRESS
- NITROSATIVE STRESS
- ESCHERICHIA-COLI
- FLAVOHEMOGLOBIN
- INHIBITION
- RESPONSES
- GLUTAMATE
- SYNTHASE