Mesenchymal stem cells (MSCs) have been widely studied for their applications in stem cell-based regeneration. During myocardial infarction (MI), infiltrated macrophages have pivotal roles in inflammation, angiogenesis and cardiac remodeling. We hypothesized that MSCs may modulate the immunologic environment to accelerate regeneration. This study was designed to assess the functional relationship between the macrophage phenotype and MSCs. MSCs isolated from bone marrow and bone marrow-derived macrophages (BMDMs) underwent differentiation induced by macrophage colony-stimulating factor. To determine the macrophage phenotype, classical M1 markers and alternative M2 markers were analyzed with or without co-culturing with MSCs in a transwell system. For animal studies, MI was induced by the ligation of the rat coronary artery. MSCs were injected within the infarct myocardium, and we analyzed the phenotype of the infiltrated macrophages by immunostaining. In the MSC-injected myocardium, the macrophages adjacent to the MSCs showed strong expression of arginase-1 (Arg1), an M2 marker. In BMDMs co-cultured with MSCs, the M1 markers such as interleukin-6 (IL-6), IL-1β, monocyte chemoattractant protein-1 and inducible nitric oxide synthase (iNOS) were significantly reduced. In contrast, the M2 markers such as IL-10, IL-4, CD206 and Arg1 were markedly increased by co-culturing with MSCs. Specifically, the ratio of iNOS to Arg1 in BMDMs was notably downregulated by co-culturing with MSCs. These results suggest that the preferential shift of the macrophage phenotype from M1 to M2 may be related to the immune-modulating characteristics of MSCs that contribute to cardiac repair.

Despite the worldwide effect of the Coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased Th2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation is associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of FcγR signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.

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We report here on the case of a child who was infected with scrub typhus, and we made the diagnosis according to the serology and by performing PCRs on the child's eschar. The patient was treated with azithromycin, and he did not experience any complications. Performing nested PCR on the eschar might be both a rapid diagnostic test for scrub typhus in the early acute stage and a differential test as to whether or not a scab is a scrub typhus eschar. CASE REPORTA 7-year-old boy was admitted to Seonam University Hospital because of his 7-day history of a high fever and rash. The physical examination at the time of admission revealed a papulomacular skin rash on his trunk that soon spread to his extremities. Enlarged tender lymph nodes were palpable in his right neck and back of the neck areas. The body temperature was 39°C, the heart rate was 115/min, and the respiration rate was 28. The patient's leukocyte count was 5,700/mm 3 (68.5% polymorphonuclear cells and 23.9% lymphocytes), his hemoglobin level was 11.2 g/dl, and the platelet count was 91,000/mm 3 . Other laboratory values were as follows: aspartate aminotransferase, 170 U/liter; alanine aminotransferase, 189 U/liter; lactate dehydrogenase, 230 U/liter; and creatine phosphokinase, 255 U/liter. We suspected that the patient was suffering from viral exanthema or infectious mononucleosis with a mobiliform rash. The patient was treated symptomatically with acetaminophen. Over the next 2 days, dyspnea developed and his temperature increased to 39.8°C. Radiographs of the chest showed an interstitial pneumonia pattern. On the third hospital day, we inadvertently found an eschar-like crust lesion on the front part of the scalp (Fig. 1), but his mother insisted that the crust was caused by minor trauma. We carefully took the history once again. Seven days before admission, he had played with his brother on the grass of Citizen's Park in Gwangju City. We wanted to know whether the crust was eschar or not. An informed consent was obtained to take a sample of the eschar and blood samples, and then a piece of crust was removed from the scalp. We immersed the crust into about 1 ml of saline. We performed nested PCR for the gene that encodes the 56-kDa protein that is specific for Orientia tsutsugamushi. Based on the clinical diagnosis of scrub typhus, azithromycin therapy was initiated. Defervescence occurred within 12 h. However, because the optimal dosage of azithromycin for the treatment of scrub typhus has not been determined, especially for children, we added another 500 mg of azithromycin at 24 h after the first dose to experimentally reduce the risk of relapse or therapeutic failure. Sixty hours after the azithromycin administration was stopped, a fever of 38.0°C, malaise, and headache were again developed. The therapy with azithromycin was restarted. Azithromycin (250 mg) once a day for an additional 5 days was added. After this administration, his symptoms, such as fever and malaise, were relieved and he was discharged without complications. A second serology f...