Background:The novel coronavirus disease 2019 (COVID-19) first broke out in Wuhan, China, spread over 227 countries and caused approximately 0.3 million death worldwide. Several biomolecules have been explored for possible biomarkers for prognosis outcome. Although increased C reactive protein (CRP) is associated with death due to COVID-19 infections, results from different populations remain inconsistent. For a conclusive result, the present meta-analysis was performed. Methods: We conducted a literature search in PubMed and Scopus database for the association of CRP concentration with COVID-19 disease outcomes. A total of 16 eligible studies were enrolled in the present analysis comprising of 1896 survivors and 849 non-survivors cases. Concentrations of CRP were compared and analyzed by a meta-analysis. Results: Egger's regression analysis (intercept = 0.04, P = 0.98, 95%CI = −5.48 to 5.58) and funnel plot revealed an absence of publication bias in the included studies. Due to the presence of significant heterogeneity across the studies (Q = 252.03, P heterogeneity = 0.000, I 2 = 93.65) random model was used for the analysis of the present study. The results of the meta-analysis demonstrated a significant role of CRP in COVID-19 infection outcome (Standard difference in means = 1.371, P = 0.000). Conclusions: Concentrations of CRP remained high in patients who died of COVID-19 infection and could be a promising biomarker for assessing disease lethality.

The pathogenesis of experimental cerebral malaria (ECM) is an immunologic process, mediated in part by Th1 CD4+ T cells. However, the role of the Th1 CD4+ T cell differentiation program on the ability to control parasitemia and susceptibility to ECM disease during blood stage malaria has never been assessed directly. Using the Plasmodium berghei ANKA murine model of ECM and mice deficient for the transcription factor T-bet (the master regulator of Th1 cells) on the susceptible C57BL/6 background, we demonstrate that although T-bet plays a role in the regulation of parasite burden, it also promotes the pathogenesis of ECM. T-bet−deficient (Tbx21−/−) mice had higher parasitemia than wild type controls did during the ECM phase of disease (17.7 ± 3.1% versus 10.9 ± 1.5%). In addition, although 100% (10/10) of wild type mice developed ECM by day 9 after infection, only 30% (3/10) of Tbx21−/− mice succumbed to disease during the cerebral phase of infection. Resistance to ECM in Tbx21−/− mice was associated with diminished numbers of IFN-γ–producing CD4+ T cells in the spleen and a lower accumulation of CD4+ and CD8+ T cells in the brain. An augmented Th2 immune response characterized by enhanced production of activated GATA-3+ CD4+ T cells and elevated levels of the eotaxin, MCP-1, and G-CSF cytokines was observed in the absence of T-bet. Our results suggest that in virulent malarias, immune modulation or therapy resulting in an early shift toward a Th2 response may help to ameliorate the most severe consequences of malaria immunopathogenesis and the prospect of host survival.

Several Plasmodium species exhibit a strong age-based preference for the red blood cells (RBC) they infect, which in turn is a major determinant of disease severity and pathogenesis. The molecular basis underlying this age constraint on the use of RBC and its influence on parasite burden is poorly understood. CD47 is a marker of self on most cells, including RBC, which, in conjunction with signal regulatory protein alpha (expressed on macrophages), prevents the clearance of cells by the immune system. In this report, we have investigated the role of CD47 on the growth and survival of nonlethal Plasmodium yoelii 17XNL (PyNL) malaria in C57BL/6 mice. By using a quantitative biotin-labeling procedure and a GFP-expressing parasite, we demonstrate that PyNL parasites preferentially infect high levels of CD47 (CD47hi)-expressing young RBC. Importantly, C57BL/6 CD47−/− mice were highly resistant to PyNL infection and developed a 9.3-fold lower peak parasitemia than their wild-type (WT) counterparts. The enhanced resistance to malaria observed in CD47−/− mice was associated with a higher percentage of splenic F4/80+ cells, and these cells had a higher percentage of phagocytized parasitized RBC than infected WT mice during the acute phase of infection, when parasitemia was rapidly rising. Furthermore, injection of CD47-neutralizing antibody caused a significant reduction in parasite burden in WT C57BL/6 mice. Together, these results strongly suggest that CD47hi young RBC may provide a shield to the malaria parasite from clearance by the phagocytic cells, which may be an immune escape mechanism used by Plasmodium parasites that preferentially infect young RBC.

The study demonstrates, for the first time, a positive correlation between protective immunity and increased levels of filaria-specific IgA in human bancroftian filariasis. Furthermore, filaria-specific IgA appears to be an immunological window for the sex-related differences in susceptibility to infection observed in human filariasis.

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Although, a large proportion of pathogenic bacteria gets eliminated from hosts after antibiotic treatment, a fraction of population confronts against such effects and undergoes growth arrest to form persisters. Persistence in bacteria is a dormant physiological state where cells escape the effects of antimicrobials as well as other host immune defences without any genetic mutations. The state of dormancy is achieved through various complex phenomena and it is known that a gene pair named as toxin–antitoxin (TA) acts as a key player of persister cell formation where the toxin is activated either stochastically or after an environmental insult, thereby silencing the physiological processes. However, the controversial role of TA modules in persister cell formation has also been documented with reasonable clarity. Persisters may revert back from state of quiescence and regrow when conditions become favourable for their propagation. Therefore, the elimination of dormant bacteria is crucial, and currently, research interest is highly focussed on developing several antipersister strategies that may kill persister bacteria by targeting different molecules. It is worth examining these targets to develop appropriate therapeutic interventions against bacterial infections and it is believed that earmarking TA system can be a novel approach for resuscitation of persisters. In this review, we discussed the role of TA modules in mediating persistence with highlighting on the debatable issues regarding contribution of these modules in dormant bacteria formation. Furthermore, we discussed if these modules in bacteria can be targeted for successful elimination of dormant persister cells.

Salmonella enterica subsp. I serovar Enteritidis (S. Enteritidis), one of the causative agents for non-typhoidal gastrointestinal diseases in humans is an intracellular bacterium and mechanism for its invasion into host cells is critical to cause infection. The virulence of the pathogen is explained by the expression of genes located on its pathogenicity islands, mostly encoded under SPI-1 and SPI-2. However, S. Typhimurium SL1344, despite sharing ∼98% of its genome with S. Enteritidis P125109, lacks few regions of differences (ROD) that are hypothesized to impart virulence potential to S. Enteritidis. In this study, we created different mutants in the ROD9 island of S. Enteritidis, also referred as SPI-19 and identified a novel locus, SEN1005, encoding a hypothetical protein that is involved in its pathogenesis. ΔSEN1005 displayed significantly reduced entry into cultured epithelial cells as well as uptake by macrophages and failed to cause acute colitis in C57BL/6 mice at day 3 post-infection (p.i.). Additionally, the global transcriptome analysis revealed a highly repressed SPI-1 and other down-regulated genes responsible for flagellar assembly, chemotaxis and motility in the mutant which correlated with decreased invasion and abated inflammation as compared to the wild-type. Therefore, our findings revealed that ΔSEN1005 was attenuated in vitro as well as in vivo and we propose this hypothetical protein to play a role in altering the expression of genes involved in Salmonella virulence.

CD4+ Keywords: IgG1 r Immunity r Plasmodium yoelii r T-bet Additional supporting information may be found in the online version of this article at the publisher's web-site