BACKGROUND: Q fever is caused by Coxiella burnetii, a bacterium that persists in M2-polarized macrophages. We wondered whether the concept of M1/M2 polarization is applicable to Q fever patients. METHODS: Monocytes from healthy controls were cultured with IFN-γ and IL-4, agonists of M1 and M2 macrophages, respectively, and their gene expression was assessed using whole-genome microarrays. Selected biomarkers were assessed in blood from Q fever patients by real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Monocytes exhibited early (6-hour) patterns of activation specific to IFN-γ or IL-4 and a late (18-hour) pattern of common activation. Because these responses were not reducible to M1/M2 polarization, we selected biomarkers and tested their relevance in Q fever patients. The early genes NLRC5, RTP4, and RHOH, which were modulated in response to IFN-γ, were up-regulated in patients with acute Q fever, and the expression levels of the late genes ALOX15, CLECSF1, CCL13, and CCL23 were specifically increased in patients with Q fever endocarditis. The RHOH and ALOX15 genes were associated with the activity of acute Q fever and Q fever endocarditis, respectively. CONCLUSIONS: Our results show that the kinetic model of monocyte activation enables a dynamic approach for the evaluation of Q fever patients.
BACKGROUND: Q fever is caused by Coxiella burnetii, a bacterium that persists in M2-polarized macrophages. We wondered whether the concept of M1/M2 polarization is applicable to Q feverpatients. METHODS: Monocytes from healthy controls were cultured with IFN-γ and IL-4, agonists of M1 and M2 macrophages, respectively, and their gene expression was assessed using whole-genome microarrays. Selected biomarkers were assessed in blood from Q feverpatients by real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Monocytes exhibited early (6-hour) patterns of activation specific to IFN-γ or IL-4 and a late (18-hour) pattern of common activation. Because these responses were not reducible to M1/M2 polarization, we selected biomarkers and tested their relevance in Q feverpatients. The early genes NLRC5, RTP4, and RHOH, which were modulated in response to IFN-γ, were up-regulated in patients with acute Q fever, and the expression levels of the late genes ALOX15, CLECSF1, CCL13, and CCL23 were specifically increased in patients with Q fever endocarditis. The RHOH and ALOX15 genes were associated with the activity of acute Q fever and Q fever endocarditis, respectively. CONCLUSIONS: Our results show that the kinetic model of monocyte activation enables a dynamic approach for the evaluation of Q feverpatients.
Authors: Talita D Fernandes; Larissa D Cunha; Juliana M Ribeiro; Liliana M Massis; Djalma S Lima-Junior; Hayley J Newton; Dario S Zamboni Journal: Infect Immun Date: 2016-08-19 Impact factor: 3.441
Authors: Emma E Davenport; Richard D Antrobus; Patrick J Lillie; Sarah Gilbert; Julian C Knight Journal: J Mol Med (Berl) Date: 2014-10-28 Impact factor: 4.599
Authors: Matheus Becker; Marco A De Bastiani; Mariana M Parisi; Fátima T C R Guma; Melissa M Markoski; Mauro A A Castro; Mark H Kaplan; Florencia M Barbé-Tuana; Fábio Klamt Journal: Sci Rep Date: 2015-08-25 Impact factor: 4.379