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Inflammatory mechanisms were recently identified as contributors to delayed neuronal damage after ischemic stroke. However, therapeutic strategies are still lacking, probably related to the outstanding standardization on inflammatory cell recruitment emerging from predominantly artificial stroke models, and the uncertainty on functional properties of distinct subpopulations. Using a rodent model of stroke that closely reflects human embolic ischemia, this study was focused on the local recruitment of immunoreactive cells as well as their functional and regional characterization. Wistar rats underwent thromboembolic middle cerebral artery occlusion, followed by intravenous injection of the blood–brain barrier permeability marker fluorescein-conjugated albumin at 24 h. One hour later, brain tissue was subjected to multi-parameter flow cytometry and Pappenheim staining to characterize cells invaded into the ischemia-affected hemisphere, compared to the contralateral side. Immunofluorescence labeling was applied to explore the distribution patterns of recruited cells and their spatial relationships with the vasculature. One day after ischemia onset, a 6.12-fold increase of neutrophils and a 5.43-fold increase of monocytes/macrophages was found in affected hemispheres, while these cells exhibited enhanced major histocompatibility complex class II expression and allocation with vessels exhibiting impaired blood–brain barrier integrity. Microglia remained numerically unaltered in ischemic hemispheres, but shifted to an activated phenotype indicated by CD45/CD86 expression and morphological changes toward an ameboid appearance in the bordering zone. Ischemia caused an increase of lymphoid cells in close vicinity to the affected vasculature, while further analyses allowed separation into natural killer cells, natural killer T cells, T cells (added by an unconventional CD11b + /CD3 + population) and two subpopulations of B cells. Taken together, our study provides novel data on the local inflammatory response to experimental thromboembolic stroke. As concomitantly present neutrophils, monocytes/macrophages and lymphoid cells in the early stage after ischemia induction correspond to changes seen in human stroke, future stroke research should preferably use animal models with relevance for clinical translation. [ABSTRACT FROM AUTHOR]

Abstract: Cellular recruitment and degeneration of branchial mitochondrion-rich (MR) cells were examined in Mozambique tilapia transferred from hypoosmotic to hyperosmotic water. To examine apoptosis in the gills associated with salinity change, tilapia were directly transferred from freshwater to 70% seawater. The TUNEL assay showed that apoptotic cells in the gills were significantly increased at 1day after transfer, which was supported by an electron-microscopic observation that gill MR cells underwent morphological changes characteristic of apoptosis such as an irregularly shaped electron-dense nucleus and distension of the tubular system. To further examine MR–cell recruitment, freshwater-acclimated tilapia were transferred either to freshwater or to 70% seawater after BrdU injection. Immunohistochemical detection of BrdU-labeled nuclei and Na+/K+-ATPase-rich MR cells allowed us to classify BrdU-labeled MR cells into two subtypes: a single MR cell and an MR–cell complex. Although newly generated single MR cells were observed similarly in both freshwater and 70% seawater-transferred fish, the density of MR–cell complexes was much higher in 70% seawater than in freshwater. Our findings indicated that transfer from hypoosmotic to hyperosmotic water enhanced apoptosis of freshwater-type MR cells, resulting in reduction in hyperosmoregulatory ability for freshwater adaptation, and stimulated the recruitment of MR–cell complexes to develop hypoosmoregulatory ability for seawater adaptation. [Copyright &y& Elsevier]

Abstract: Type I IFN is key to the immune response to viral pathogens, however its role in bacterial infections is less well understood. Mice lacking the type I IFN receptor (IFNAR−/−) demonstrate enhanced resistance to infection with Listeria monocytogenes. We have now determined that following infection with Listeria, the composition of innate cells recruited to the peritoneal cavity of IFNAR−/− mice reflects an increase in the frequency of neutrophils and a decrease in monocyte frequency compared to WT controls. These differences in inflammatory infiltrates could not be attributed to distinct bone marrow composition prior to infection or to level of apoptosis. We also observed no differences in neutrophil oxidative burst. However, blocking CXCR2 prevented enhanced neutrophil influx and hampered bacterial clearance. Taken together, these studies highlight a novel mechanism by which type I interferon signaling regulates the immune response to Listeria, through negative regulation of chemokines driving neutrophil recruitment. [Copyright &y& Elsevier]

Type I IFN is key to the immune response to viral pathogens, however its role in bacterial infections is less well understood. Mice lacking the type I IFN receptor (IFNAR−/−) demonstrate enhanced resistance to infection with Listeria monocytogenes . We have now determined that following infection with Listeria, the composition of innate cells recruited to the peritoneal cavity of IFNAR−/− mice reflects an increase in the frequency of neutrophils and a decrease in monocyte frequency compared to WT controls. These differences in inflammatory infiltrates could not be attributed to distinct bone marrow composition prior to infection or to level of apoptosis. We also observed no differences in neutrophil oxidative burst. However, blocking CXCR2 prevented enhanced neutrophil influx and hampered bacterial clearance. Taken together, these studies highlight a novel mechanism by which type I interferon signaling regulates the immune response to Listeria , through negative regulation of chemokines driving neutrophil recruitment. [ABSTRACT FROM AUTHOR]

Abstract: Experimental models of infection with Leishmania spp. have provided knowledge of several immunological events involved in the resistance mechanism used by the host to restrain parasite growth. It is well accepted that concomitant immunity exists, and there is some evidence that it would play a major role in long-lasting acquired resistance to infection. In this paper, the resistance to Leishmania amazonensis infection in C57BL/6 mice infected with Leishmania major was investigated. C57BL/6 mice, which spontaneously heal lesions caused by infection with L. major, were infected with L. amazonensis at different times before and after L. major. We demonstrated that C57BL/6 mice previously infected with L. major restrain pathogenic responses induced by L. amazonensis infection and decrease parasite burdens by one order of magnitude. Co-infected mice showed production of IFN-γ in lesions similar to mice infected solely with L. major, but higher TNF-α and nitric oxide synthase (iNOS) mRNA expression was observed. Surprisingly, the restrained pathogenic response was not related to IL-10 production, as evidenced by lower levels of both mRNA, protein expression in lesions from co-infected mice and in co-infections in IL-10−/− mice. Examination of the inflammatory infiltrate at the site of infection showed a reduced number of monocytes and lymphocytes in L. amazonensis lesions. Additionally, differential production of the CCL3/MIP-1α and CCL5/RANTES was observed. We suggest that the control of lesion progression caused by L. amazonensis in C57BL/6 mice pre-infected with L. major is related to the induction of a down-regulatory environment at the site of infection with L. amazonensis. [Copyright &y& Elsevier]

Abstract: Leishmania amazonensis infection, occurring predominantly in Central and South America, can manifest itself in several forms, including those of cutaneous and diffuse cutaneous leishmaniasis. The outcome of L. amazonensis infection depends largely on host immune responses to the parasites. While CD4+ T cell activation is a prerequisite for pathogenesis in L. amazonensis-infected mice, the roles of B cells and their antibody production are unclear. In this study, we provide evidence suggesting that B cells and antibodies are involved in disease pathogenesis. We documented a correlation between B cell activation and lesion progress in immunocompetent mice. In the absence of functional B cells and antibodies, JhD mice showed a delayed onset of disease and developed small lesions. Histological examination of these mice revealed a significant reduction in CD4+ and CD8+ T cells, but not in MAC1+ macrophages, at the infection site. In contrast to the wild-type mice that showed typical tissue necrosis, L. amazonensis-infected JhD mice showed no or minimal signs of necrotic foci. A marked reduction in CD4+ T cell proliferation and cytokine (IFN-γ and IL-10) production in infected JhD mice suggested an involvement of B cells and antibodies in the priming of parasite-specific T cells. This notion was further supported by the observations that adoptive transfer of B cells or antibodies could restore CD4+ T cell activation and migration in infected JhD mice. Moreover, antibody coating of parasites could stimulate dendritic cells to produce high levels of cytokines and increase their ability to prime naı¨ve CD4+ T cells. Since CD4+ T cells are crucial to disease pathogenesis, this study suggests that B cells and their antibody production enhanced L. amazonensis infection, partially by promoting T cell priming and cellular migration to the infection site. [Copyright &y& Elsevier]