Universität zu Köln

Tosetti, Bettina, Ward, Beate, Grumme, Daniela, Herb, Marc ORCID: 0000-0002-7533-0288, Schramm, Michael, Utermoehlen, Olaf, Heukamp, Lukas C., Kroenke, Martin and Krut, Oleg (2021). NOX2 Deficiency Permits Sustained Survival of S. aureus in Macrophages and Contributes to Severity of Infection. Front. Immunol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

Full text not available from this repository.

Abstract

Although the crucial role of professional phagocytes for the clearance of S. aureus infections is well-established, several studies indicate an adverse role of leukocytes in the dissemination of S. aureus during infection. Since only little is known about macrophages in this context, we analyzed the role of macrophages, and in particular reactive oxygen species deficiency, for the seeding of S. aureus metastases. Infection of bone marrow-derived macrophages (BMDM) with S. aureus revealed that NADPH oxidase 2 (NOX2-) deficient, but not NOX1- or NOX4-deficient, BMDM failed to clear intracellular S. aureus. Despite of larger intracellular bacterial burden, NOX2-deficient BMDM showed significantly improved survival. Intravenous injection of mice with in vitro-infected BMDMs carrying intracellular viable S. aureus led to higher bacterial loads in kidney and liver of mice compared to injection with plain S. aureus. An even higher frequency of liver abscesses was observed in mice infected with S. aureus-loaded nox2(-/-) BMDM. Thus, the improved intracellular survival of S. aureus and improved viability of NOX2-deficient BMDM is associated with an aggravated metastatic dissemination of S. aureus infection. A combination of vancomycin and the intracellularly active antibiotic rifampicin led to complete elimination of S. aureus from liver within 48 h, which was not achieved with vancomycin treatment alone, underscoring the impact of intracellular S. aureus on the course of disease. The results of our study indicate that intracellular S. aureus carried by macrophages are sufficient to establish a systemic infection. This suggests the inclusion of intracellularly active antibiotics in the therapeutic regimen of invasive S. aureus infections, especially in patients with NADPH oxidase deficiencies such as chronic granulomatous disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tosetti, Bettina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ward, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Grumme, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Herb, Marc UNSPECIFIED orcid.org/0000-0002-7533-0288 UNSPECIFIED Schramm, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Krut, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-581591
DOI:	10.3389/fimmu.2021.633629
Journal or Publication Title:	Front. Immunol.
Volume:	12
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTRACELLULAR STAPHYLOCOCCUS-AUREUS; CHRONIC GRANULOMATOUS-DISEASE; MECHANISMS; PHAGOCYTOSIS; PERSISTENCE; DESTRUCTION; NEUTROPHILS; BACTEREMIA; DEFENSINS; ZEBRAFISH Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58159