Intranasal (i.n.) instillation of different amounts of purified Stenotrophomonas maltophilia flagellin preparation (1, 5 and 15 mg) in BALB/c mice stimulated a transient innate immune response in the lungs. This was characterized by infiltration of different kinds of leukocytes (neutrophils, monocytes and lymphocytes), production of various inflammatory mediators (tumour necrosis factor alpha, interleukin 1 beta, interleukin 10, nitric oxide, myeloperoxidase and malondialdehyde) and activated alveolar macrophages (AMs). The proinflammatory cytokine production resulted in accumulation of activated neutrophils and macrophages and their products following immunostimulation with flagellin. The activation of AMs by flagellin was non-specific as AMs obtained from flagellin-treated animals, even after 4 h of exposure, were found to engulf and kill S. maltophilia and Staphylococcus aureus efficiently compared to macrophages obtained from control animals. i.n. instillation of 5 mg flagellin resulted in the generation of an effective innate immunity compared to other flagellin doses. Our data provide strong evidence that S. maltophilia flagellin stimulates innate immunity in mouse lung.
Chronic hepatitis B involves different immune cells. The direct role of antibody-secreting B cells in the severity of chronic hepatitis B unclear. In this study, the number of plaque forming cells [PFC-(IgG, IgM, anti-HBc IgG, and anti-HBc IgM)], liver function tests (LFT) [alkaline phosphatase (ALP), alanine aminotransferase (ALT), and total serum bilirubin (TSB)], the levels of IL-10 in sera and in lymphocyte cultures, the number of CD4(+) and CD8(+) cells were measured in the peripheral blood of patients and in the controls. In addition, the hepatocytotoxic effect of anti-HBc and anti-HBe in vitro was studied. The largest number of PFCs was observed in the peripheral blood of patients with chronic hepatitis B. This was concomitant with a decrease in CD4(+) /CD8(+) ratio versus this ratio in asymptomatic HBV carriers and in healthy volunteers (P < 0.05). An increase in immunoglobulin (IgG and IgM) levels, anti-HBc IgG, and anti-HBc IgM levels and LFTs in peripheral blood of patients with chronic hepatitis B was seen. Anti-HBc induced hepatocytotoxicity in vitro. The expression of mRNA and protein for IL-10 production was observed at a significant level in culture of lymphocytes isolated from patients with chronic hepatitis B. In addition, a high level of IL-10 was found only in the sera of patients with chronic hepatitis B. It is concluded that the antibody-secreting B cells and the antibodies, which are produced, play an important role in the severity of chronic hepatitis B, which was related negatively with CD4(+) /CD8(+) ratio and positively with IL-10 expression.
A comprehensive study on the production of inflammatory mediators in the lungs of BALB/c mice following infection with Stenotrophomonas maltophilia was conducted. The levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were raised in the lungs of infected mice compared with control. The production of anti-inflammatory cytokine IL-10 was slightly delayed. Its peak level was on the 2 nd day, whereas the peak of pro-inflammatory cytokines was observed on day 1 after intranasal challenge. This was accompanied by a rise in myeloperoxidase (MPO) and malondialdehyde (MDA) on day 1. The increase in MPO levels matched with histopathological observations, as neutrophils infiltration was detected on the first day. Alveolar macrophages (AMs) obtained from infected animals showed a higher rate of uptake and killing when exposed to bacteria in vitro, compared with similar experiments conducted with AMs from normal mice (control). This suggests that AMs were more efficient in cleaning the bacteria. The nitric oxide (NO) production however started early during infection but reached its maximum on the 3 rd day. No mortality was observed among the infected animals, and infection was resolved by the 5 th day post infection. No drastic changes in the lung tissue were observed on histopathological examination.
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