Possible Role of Pineal and Extra-Pineal Melatonin in Surveillance, Immunity, and First-Line Defense.

Melatonin is a highly conserved molecule found in prokaryotes and eukaryotes that acts as the darkness hormone, translating environmental lighting to the whole body, and as a moderator of innate and acquired defense, migration, and cell proliferation processes. This review evaluates the importance of pineal activity in monitoring PAMPs and DAMPs and in mounting an inflammatory response or innate immune response. Activation of the immune-pineal axis, which coordinates the pro-and anti-inflammatory phases of an innate immune response, is described. PAMPs and DAMPs promote the immediate suppression of melatonin production by the pineal gland, which allows leukocyte migration. Monocyte-derived macrophages, important phagocytes of microbes, and cellular debris produce melatonin locally and thereby initiate the anti-inflammatory phase of the acute inflammatory response. The role of locally produced melatonin in organs that directly contact the external environment, such as the skin and the gastrointestinal and respiratory tracts, is also discussed. In this context, as resident macrophages are self-renewing cells, we explore evidence indicating that, besides avoiding overreaction of the immune system, extra-pineal melatonin has a fundamental role in the homeostasis of organs and tissues.

The Role of Macrophages in the Host's Defense against Sporothrix schenckii.

The role of immune cells associated with sporotrichosis caused by Sporothrix schenckii is not yet fully clarified. Macrophages through pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) of Sporothrix, engulf it, activate respiratory burst, and secrete pro-inflammatory or anti-inflammatory biological mediators to control infection. It is important to consider that the characteristics associated with S. schenckii and/or the host may influence macrophage polarization (M1/M2), cell recruitment, and the type of immune response (1, 2, and 17). Currently, with the use of new monocyte-macrophage cell lines, it is possible to evaluate different host-pathogen interaction processes, which allows for the proposal of new mechanisms in human sporotrichosis. Therefore, in order to contribute to the understanding of these host-pathogen interactions, the aim of this review is to summarize and discuss the immune responses induced by macrophage-S. schenckii interactions, as well as the PRRs and PAMPs involved during the recognition of S. schenckii that favor the immune evasion by the fungus.

Isolation and Phenotypic Characterization of Inflammatory Cells from Clinical Samples: Purification of Macrophages from Trypanosoma cruzi-Infected Hearts.

Trypanosoma cruzi, the causal agent of chronic Chagas cardiomyopathy, exhibits an important tropism for cardiac tissue. In consequence, T. cruzi experimental infection represents a unique model to study cardiac macrophage behavior and effector functions during either acute or chronic immune response. In this chapter we describe a protocol to isolate immune cells from T. cruzi-infected murine cardiac tissue and to determine the percentage, absolute number, phenotype, and functionality of monocytes and macrophages by using flow cytometry. Moreover, we describe the parameters to discriminate between resident and infiltrating mononuclear phagocytic cells within infected hearts. The investigations in this field will provide mechanistic insights about the roles of these innate immune cells in the context of a clinically relevant target tissue.

Chronic inflammation in skeletal muscle impairs satellite cells function during regeneration: can physical exercise restore the satellite cell niche?

Chronic inflammation impairs skeletal muscle regeneration. Although many cells are involved in chronic inflammation, macrophages seem to play an important role in impaired muscle regeneration since these cells are associated with skeletal muscle stem cell (namely, satellite cells) activation and fibro-adipogenic progenitor cell (FAP) survival. Specifically, an imbalance of M1 and M2 macrophages seems to lead to impaired satellite cell activation, and these are the main cells that function during skeletal muscle regeneration, after muscle damage. Additionally, this imbalance leads to the accumulation of FAPs in skeletal muscle, with aberrant production of pro-fibrotic factors (e.g., extracellular matrix components), impairing the niche for proper satellite cell activation and differentiation. Treatments aiming to block the inflammatory pro-fibrotic response are partially effective due to their side effects. Therefore, strategies reverting chronic inflammation into a pro-regenerative pattern are required. In this review, we first describe skeletal muscle resident macrophage ontogeny and homeostasis, and explain how macrophages are replenished after muscle injury. We next discuss the potential role of chronic physical activity and exercise in restoring the M1 and M2 macrophage balance and consequently, the satellite cell niche to improve skeletal muscle regeneration after injury.

Detection of macrophages infected with Mycobacterium avium subspecies paratuberculosis in a cow with clinical stage IV of Johne's disease. A case report / Detección de macrófagos infectados con Mycobacterium avium subspecies paratuberculosis en una vaca en fase clínica IV de la enfermedad de Johne. Reporte de un caso / Detecção de macrófagos infectados com Mycobacterium avium paratuberculosis subespécie em uma vaca com uma fase clínica IV da doença de Johne. Um relato de caso

Anamnesis: a six-year-old milking Holstein cow (Bos taurus taurus) was diagnosed with stage IV Johne's Disease (JD). Clinical and Laboratory findings: the cow suffered intermittent diarrhea during 6 months with no response to antibiotic treatment. Consequently, the cow was subjected to euthanasia. Treatment approach: antemortem milk and peripheral blood samples and postmortem colon, mediastinic, mesenteric lymph nodes, and spleen samples were processed for macrophages isolation. Total DNA was extracted from macrophages and used to diagnose IS900 of Mycobacterium avium paratuberculosis (MAP) through real time PCR. The MAP IS900 segment was successfully amplified from cells of all samples, indicating that these cells were MAP-infected macrophages. Conclusion: macrophages of cows suffering from JD can be used for amplification of the MAP IS900 segment.

Anamnesis: una vaca Holstein de 6 años de edad (Bos taurus taurus) presentó sintomatología de la fase IV de la enfermedad de Johne. Hallazgos clínicos y de laboratorio: la vaca presentó diarrea intermitente durante 6 meses sin respuesta al tratamiento con antibióticos. En consecuencia, la vaca fue sometida a eutanasia. Esquema de tratamiento: muestras de leche y de sangre periférica se tomaron ante-mortem; muestras de la mucosa del intestino, bazo y linfonodos mediastínico y mesentérico, se tomaron post-mortem, todas para aislamiento de macrófagos. El ADN total de los macrófagos fue usado para la amplificación del segmento IS900 de Mycobacterium avium paratuberculosis (MAP) por PCR en tiempo real. Conclusión: los macrófagos de vacas con la enfermedad de Johne pueden ser usados para la amplificación del segmento IS900 de MAP.

Anamnese: uma vaca Holstein com 6 anos de idade (Bos taurus taurus) apresentou os sintomas da fase IV da doença de Johne. Achados clínicos e laboratoriais: a vaca teve diarreia intermitente por seis meses sem resposta ao tratamento com antibióticos. Por conseguinte, a vaca foi submetida à eutanásia. Abordagem de tratamento: amostras de leite e de sangue periférico foram retiradas ante-mortem, enquanto as amostras da mucosa intestinal, baço e linfonodos mesentéricos e mediastinais foram tomadas todas post-mortem para o isolamento de macrófagos. O ADN total de macrófagos foi utilizado para amplificação do segmento IS900 do Mycobacterium avium paratuberculosis (MAP) por PCR em tempo real. Conclusão: macrófagos isolados a partir de vacas com doença de Johne podem ser utilizados para a amplificação da segmento IS900 do MAP.