IL-22 Is Deleterious along with IL-17 in Allergic Asthma but Is Not Detrimental in the Comorbidity Asthma and Acute Pneumonia.

There is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. To investigate the role of IL-22, we used IL-22 deficient mice (IL-22 KO) sensitized and challenged with ovalbumin (OVA) and compared with wild type (WT) animals exposed to OVA. IL-22 KO animals exposed to OVA showed a decreased number and frequency of eosinophils, IL-5 and IL-13 in the airways, reduced mucus production and pulmonary inflammation. In addition, IL-22 KO animals exhibited a decreased percentage and number of lung CD11c+CD11b+ cells and increased apoptosis of eosinophils. Th17 cell transfer generated from IL-22 KO to animals previously sensitized and challenged with OVA caused a reduction in eosinophil frequency and number in the airways compared to animals transferred with Th17 cells generated from WT mice. Therefore, IL-22 is deleterious with concomitant secretion of IL-17. Our findings show a pro-inflammatory role for IL-22, confirmed in a model of allergen-free and allergen-specific immunotherapy. Moreover, during the comorbidity asthma and pneumonia that induces neutrophil inflammation, IL-22 was not detrimental. Our results show that targeting IL-22 would negatively affect the survival of eosinophils, reduce the expansion or migration of CD11c+CD11b+ cells, and negatively regulate allergic asthma.

Refrigerated modified Knott concentrate enables long-term morphological viability of canine blood microfilariae.

There are several methods of laboratory diagnosis of filarids, the most used are the thick smear and the Knott method. Both are quick to perform, have a low cost and allow observing the presence, quantifying and analyzing the morphological characteristics of microfilariae. Knowing the morphological viability of fixed microfilariae is of practical importance, as it allows the transport of samples to a laboratory, facilitates epidemiological studies , and allows the storage of samples for didactic. Thus, the aim of this study was to evaluate the morphological viability of microfilariae fixed in the refrigerated modified knott test using 2% formalin. To perform the modified Knott technique, 10 samples of microfilaremic dogs aged over 6 months were used. To evaluate the morphological viability time of the microfilariae in the modified Knott concentrate, the evaluations were repeated after intervals of 0, 1, 7, 30, 60, 120, 180, 240, and 304 days. In the present study, we did not verify any difference in the morphology of the microfilariae in any of the analyzed intervals from day 0 to 304 days, and it is possible to conclude that the use of 2% formalin in the modified Knott technique allows the microfilariae to be identified in a period of 304 days. days after processing the sample without changes in its morphology.

Existem diversos métodos de diagnóstico laboratorial de filarídeos, os mais utilizados são a gota espessa e o método do Knott. Ambos são de rápida execução, possui baixo custo e permitem observar a presença, quantificar e analisar as características morfológicas das microfilárias. Conhecer a viabilidade morfológica das microfilárias fixadas tem importância prática, pois permite o transporte de amostras para um laboratório, facilita estudos epidemiológicos, e permite o armazenamento de amostras para fins didáticos. Desta maneira, o objetivo do trabalho foi avaliar a viabilidade morfológica das microfilárias fixadas em teste do knott modificado refrigerado utilizando formalina a 2%. Para realização da técnica de knott modificado foram utilizadas 10 amostras de cães microfilarêmicos, com idade superior a 6 meses. Para avaliar o tempo de viabilidade morfológica das microfilárias no concentrado de Knott modificado, foram repedidas as avaliações após intervalos de 0,1,7, 30, 60, 120, 180, 240 e 304 dias. No presente estudo não verificamos diferença na morfologia das microfilárias em nenhum dos intervalos analisados deste do dia 0 até 304 dias, sendo possível concluir que a utilização da formalina a 2% na técnica de Knott modificada permite que as microfilárias possam ser identificadas em período de 304 dias após o processamento da amostra sem que ocorram alterações na sua morfologia.

Cell death induced by NLRP3-palmitate axis impairs pulmonary damage tolerance and aggravates immunopathology during obesity-tuberculosis comorbidity.

A low-grade and persistent inflammation, which is the hallmark of obesity, requires the participation of NLRP3 and cell death. During Mycobacterium tuberculosis infection, NLRP3 signaling is important for bacterial killing by macrophages in vitro but was shown to be dispensable for host protection in vivo. We hypothesized that during obesity-tuberculosis (TB) comorbidity, NLRP3 signaling might play a detrimental role by inducing excessive inflammation. We employed a model of high-fat-diet-induced obesity, followed by M. tuberculosis infection in C57BL/6 mice. Obese mice presented increased susceptibility to infection and pulmonary immunopathology compared to lean mice. Using treatment with NLRP3 antagonist and Nlrp3-/- mice, we showed that NLRP3 signaling promoted cell death, with no effect in bacterial loads. The levels of palmitate were higher in the lungs of obese infected mice compared to lean counterparts, and we observed that this lipid increased M. tuberculosis-induced macrophage death in vitro, which was dependent on NLRP3 and caspase-1. At the chronic phase, although lungs of obese Nlrp3-/- mice showed an indication of granuloma formation compared to obese wild-type mice, there was no difference in the bacterial load. Our findings indicate that NLRP3 may be a potential target for host-directed therapy to reduce initial and severe inflammation-mediated disease and to treat comorbidity-associated TB. © 2022 The Pathological Society of Great Britain and Ireland.

Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection.

The microbiota of the gut-lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17- cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut-lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.