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[This corrects the article DOI: 10.3389/fphys.2022.867362.].
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Purpose: To investigate the effect of different water immersion temperatures on the kinetics of blood markers of skeletal muscle damage and the main leukocyte subpopulations. Methods: Eleven recreationally trained young men participated in four experimental sessions consisting of unilateral eccentric knee flexion and 90 min of treadmill running at 70% of peak oxygen uptake, followed by 15 min of water immersion recovery at 15, 28 or 38°C. In the control condition participants remained seated at room temperature. Four hours after exercise recovery, participants completed a performance test. Blood samples were obtained before and immediately after exercise, after immersion, immediately before and after the performance test and 24 h after exercise. The number of leukocyte populations and the percentage of lymphocyte and monocytes subsets, as well as the serum activity of creatine kinase and aspartate aminotransferase were determined. Results: Leukocytosis and increase in blood markers of skeletal muscle damage were observed after the exercise. Magnitude effect analysis indicated that post-exercise hot-water immersion likely reduced the exercise-induced lymphocytosis and monocytosis. Despite reduced monocyte count, recovery by 38°C immersion, as well as 28°C, likely increased the percentage of non-classical monocytes in the blood. The percentage of CD25+ cells in the CD4 T cell subpopulation was possibly lower after immersion in water at 28 and 15°C. No effect of recovery by water immersion was observed for serum levels of creatine kinase and aspartate aminotransferase. Conclusions: Recovery by hot-water immersion likely attenuated the leukocytosis and increased the mobilization of non-classical monocytes induced by a single session of exercise combining resistance and endurance exercises, despite no effect of water immersion on markers of skeletal muscle damage. The monocyte response mediated by hot water immersion may lead to the improvement of the inflammatory response evoked by exercise in the skeletal muscle.
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Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of Mycobacterium tuberculosis (Mtb-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after Mtb-Ag stimulation in HR-TB. We also found that LR-TB displayed the highest percentages of circulating M-MDSC. These results demonstrate that CD16 positive monocytes and M-MDSC frequencies could be used as another immunological classification parameter. Interestingly, in LR-TB, frequencies of CD16 positive monocytes and M-MDSC were restored after only three weeks of anti-TB treatment. Together, our findings show a link between the immunological status of TB patients and the levels of different circulating myeloid cell populations.
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Mycobacterium tuberculosis , Células Supressoras Mieloides , Tuberculose , Humanos , Monócitos , Células MieloidesRESUMO
BACKGROUND: Depression is a highly prevalent disorder that is one of the leading causes of disability worldwide. Despite an unknown aetiology, evidence suggests that the innate and adaptive immune systems play a significant role in the development and maintenance of major depressive disorder (MDD). The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), has demonstrated rapid and robust efficacy as an antidepressant when administered at sub-anaesthetic doses. METHODS: Our goal was to characterize the pro-inflammatory profile of patients with MDD by measuring pro-inflammatory cytokines in plasma and circulating monocyte subsets and to understand how ketamine induces an anti-inflammatory program in monocyte and macrophages in vitro and vivo. FINDING: Our results show that patients with MDD without other comorbidities (Nâ¯=â¯33) exhibited significantly higher levels of pro-inflammatory IL-12 and IL-6 in plasma and that these cytokines were associated with increased numbers of non-classical (CD11b+CD16brightCD14neg) monocytes and increased activation state (CD40+CD86+) of classical monocytes in circulation. Remarkably, we have demonstrated that sub-anaesthetic doses of ketamine programs human monocytes into M2c-like macrophages by inducing high levels of CD163 and MERTK with intermediate levels of CD64 and stimulating mTOR-associated gene expression in vitro. The NMDAR antagonist MK-801, but not the α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonist, NBQX, also polarizes macrophages to an M2c-like phenotype, but this phenotype disappears upon mTOR pathway inhibition. Sub-anaesthetic doses (10â¯mg/kg) of ketamine administration in mice both promote reduction of circulating classical pro-inflammatory monocytes and increase of alternative M2 macrophage subtypes in the spleen and CNS. INTERPRETATION: Our results suggest an anti-inflammatory property of ketamine that can skew macrophages to an M2-like phenotype, highlighting potential therapeutic implications not only for patients with MDD but also other inflammatory-based diseases. FUNDING: This study was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT-FONCYT).
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Citocinas/metabolismo , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adulto , Animais , Biomarcadores , Citocinas/sangue , Transtorno Depressivo Maior/psicologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunofenotipagem , Mediadores da Inflamação/sangue , Ketamina/metabolismo , Ketamina/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Suicídio , Adulto JovemRESUMO
BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic spinal cord injury worldwide. Surgical decompression is recommended as the preferred treatment strategy for DCM as it halts disease progression and improves neurologic symptoms. We previously demonstrated that neuroinflammation, including monocytes, plays a critical role in the pathobiology of DCM and in ischemic-reperfusion injury (IRI) following surgical decompression. Monocytes are able to enter the spinal cord and brain tissues due to damage to the blood spinal cord and blood brain barrier following injury. Studies have demonstrated that stroke patients and individuals undergoing hip replacement surgery have increased systemic levels of monocytes. Additionally, changes in the signalling responses of monocytes are associated with post-surgical recovery or with ischemic neural tissue damage. Herein, we investigated the role of systemic monocytes as a predictive biomarker for clinical recovery following decompressive surgery for DCM. FINDINGS: There was a 2-fold increase in the number of monocytes in DCM patients at 24â¯h following decompression as compared to baseline levels, which was associated with a significant improvement in the modified Japanese Orthopedic Association scale (mJOA) at 6-months after surgery (pâ¯<â¯.0001). In a mouse model of DCM, depleting acute monocytes reduced the non-classical (Ly6Clow) subset from circulation (pâ¯<â¯.05) and resulted in a 1.8-fold increase in CD11b expression in the spinal cord at 5â¯weeks following decompression. Acute monocyte depletion was accompanied by a modest decline in long-term overground locomotion, as evidenced by significantly reduced hindlimb swing speed. CONCLUSIONS: This work demonstrated that decompressive surgery leads to an acute increase in peripheral monocytes in human DCM patients, which is modestly associated with clinical recovery. We anticipate that this work could contribute to the implementation of routine measurements of blood monocyte subsets, their activation state, and production of cytokines following decompressive surgery. This information could help to select perioperative anti-inflammatory treatments that can enhance the beneficial effects of decompressive surgery and reduce the incidence of post-operative complications, while avoiding a reduction in systemic monocytes.
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Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/tendências , Monócitos/metabolismo , Recuperação de Função Fisiológica/fisiologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Descompressão Cirúrgica/efeitos adversos , Feminino , Humanos , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Distribuição Aleatória , Estudos RetrospectivosRESUMO
Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non-classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non-classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non-classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor-α+ cells and exposure of phosphatidylserine, were recorded in the non-classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non-classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin-6 (IL-6), IL-8 and IL-10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non-classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor-α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non-classical monocytes seem to be associated with the immunopathology of dengue infection.