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Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype. Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration. Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates. We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10. Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers. The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA. Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C. Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization. Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Santana, Righetti, Breda, Domínguez-Amorocho, Ramalho, Dantas, Nunes, Tibério, Soriano, Câmara, Quintão and Cazita.)

Sepsis is well known to cause a high patient death rate (up to 50%) during the intensive care unit (ICU) stay. In addition, sepsis survival patients also exhibit a very high death rate after hospital discharge compared to patients with any other disease. The addressed question is then: why septic patients remain ill after hospital discharge? The cellular and molecular mechanisms involved in the high rate of septic patient deaths are still unknown. We described herein the studies that investigated the percentage of septic patients that died after hospital discharge ranging from 90 days up to 5 years. We also reported the symptoms of septic patients after hospital discharge and the development of the recently called post-sepsis syndrome (PSS). The most common symptoms of the PSS are cognitive disabilities, physical functioning decline, difficulties in performing routine daily activities, and poor life quality. The PSS also associates with quite often reinfection and re-hospitalization. This condition is the cause of the high rate of death mentioned above. We reported the proportion of patients dying after hospital discharge up to 5 years of followed up and the PSS symptoms associated. The authors also discuss the possible cellular and metabolic reprogramming mechanisms related with the low survival of septic patients and the occurrence of PSS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gritte, Souza-Siqueira, Curi, Machado and Soriano.)

Objectives: To compare microscopic and immunologic features in the spleens of patients who died of pulmonary hemorrhage and shock caused by leptospirosis (11 cases) or Gram-positive/-negative bacterial septic shock (10 cases) to those from control spleens (12 cases from splenectomy). Methodology: Histological features in the red pulp and white pulp were analyzed using archived samples by a semi quantitative score. Immunohistochemistry was used for the recognition of immune cell markers, cytokines, caspase-3 and Leptospira antigens. Results: The control group differed significantly from the leptospirosis and septic shock patients which demonstrate strong similarities: diffuse congestion in the red pulp with a moderate to intense infiltration of plasma cells and polymorphonuclear cells; follicles with marked atrophy; high density of CD20 + cells; low density of NK, TCD4 + and active caspase-3 positive cells and strong expression of IL-10; leptospirosis patients had higher S100 and TNF-α positive cells in the spleen than the other groups. Conclusion: The results suggest that an immunosuppressive state develops at the terminal stage of severe leptospirosis with pulmonary hemorrhage and shock similar to that of patients with septic shock, with diffuse endothelial activation in the spleen, splenitis, and signs of disturbance in the innate and adaptive immunity in the spleen. The presence of leptospiral antigens in 73% of the spleens of the leptospirosis patients suggests the etiological agent contributes directly to the pathogenesis of the lesions. Our results support therapeutic approaches involving antibiotic and immunomodulatory treatments for leptospirosis patients and suggest that leptospirosis patients, which are usually young men with no co-morbidities, form a good group for studying sepsis and septic shock.