Dataset Information

The uptake of apoptotic cells drives Coxiella burnetii replication and macrophage polarization: a model for Q fever endocarditis.

ABSTRACT: Patients with valvulopathy have the highest risk to develop infective endocarditis (IE), although the relationship between valvulopathy and IE is not clearly understood. Q fever endocarditis, an IE due to Coxiella burnetii, is accompanied by immune impairment. Patients with valvulopathy exhibited increased levels of circulating apoptotic leukocytes, as determined by the measurement of active caspases and nucleosome determination. The binding of apoptotic cells to monocytes and macrophages, the hosts of C. burnetii, may be responsible for the immune impairment observed in Q fever endocarditis. Apoptotic lymphocytes (AL) increased C. burnetii replication in monocytes and monocyte-derived macrophages in a cell-contact dependent manner, as determined by quantitative PCR and immunofluorescence. AL binding induced a M2 program in monocytes and macrophages stimulated with C. burnetii as determined by a cDNA chip containing 440 arrayed sequences and functional tests, but this program was in part different in monocytes and macrophages. While monocytes that had bound AL released high levels of IL-10 and IL-6, low levels of TNF and increased CD14 expression, macrophages that had bound AL released high levels of TGF-beta1 and expressed mannose receptor. The neutralization of IL-10 and TGF-beta1 prevented the replication of C. burnetii due to the binding of AL, suggesting that they were critically involved in bacterial replication. In contrast, the binding of necrotic cells to monocytes and macrophages led to C. burnetii killing and typical M1 polarization. Finally, interferon-gamma corrected the immune deactivation induced by apoptotic cells: it prevented the replication of C. burnetii and re-directed monocytes and macrophages toward a M1 program, which was deleterious for C. burnetii. We suggest that leukocyte apoptosis associated with valvulopathy may be critical for the pathogenesis of Q fever endocarditis by deactivating immune cells and creating a favorable environment for bacterial persistence.

SUBMITTER: Benoit M

PROVIDER: S-EPMC2361190 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The uptake of apoptotic cells drives Coxiella burnetii replication and macrophage polarization: a model for Q fever endocarditis.

Benoit Marie M Ghigo Eric E Capo Christian C Raoult Didier D Mege Jean-Louis JL

PLoS pathogens 20080516 5

Patients with valvulopathy have the highest risk to develop infective endocarditis (IE), although the relationship between valvulopathy and IE is not clearly understood. Q fever endocarditis, an IE due to Coxiella burnetii, is accompanied by immune impairment. Patients with valvulopathy exhibited increased levels of circulating apoptotic leukocytes, as determined by the measurement of active caspases and nucleosome determination. The binding of apoptotic cells to monocytes and macrophages, the h ...[more]

PMID: 18483547

Similar Datasets

Project description:Coxiella burnetii is the causative bacterium of the zoonotic disease Q fever, which is recognised as a public health concern globally. Macropods have been suggested as a potential source of C. burnetii infection for humans. The aim of this cross-sectional study was to determine the prevalence of C. burnetii exposure in a cohort of Australian wildlife rehabilitators (AWRs) and assess Q fever disease and vaccination status within this population. Blood samples were collected from adult participants attending the Australian Wildlife Rehabilitation Conference in Sydney in July 2018. Participants completed a questionnaire at the time of blood collection. Antibody titres (IgG, IgA and IgM) against phase I and phase II C. burnetii antigens as determined by immunofluorescence assay, revealed that of the unvaccinated participants, 6.1% (9/147) had evidence of exposure to C. burnetii. Of the total participants, 8.1% (13/160) had received Q fever vaccination, four of whom remained seropositive at the time of blood collection. Participants reporting occupational contact with ruminants, were eight times more likely to have been vaccinated against Q fever, than those reporting no occupational animal contact (OR 8.1; 95% CI 1.85-45.08). Three AWRs (2%) reported having had medically diagnosed Q fever, two of whom remained seropositive at the time of blood collection. Despite the lack of association between macropod contacts and C. burnetii seropositivity in this cohort, these findings suggest that AWRs are approximately twice as likely to be exposed to C. burnetii, compared with the general Australian population. This provides support for the recommendation of Q fever vaccination for this potentially 'at-risk' population. The role of macropods in human Q fever disease remains unclear, and further research into C. burnetii infection in macropods including: infection rate and transmission cycles between vectors, macropods as reservoirs, other animals and humans is required.

Dataset Information

The uptake of apoptotic cells drives Coxiella burnetii replication and macrophage polarization: a model for Q fever endocarditis.

Publications

The uptake of apoptotic cells drives Coxiella burnetii replication and macrophage polarization: a model for Q fever endocarditis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets