Pathogens and Immunity最新文献

Background: Uropathogenic Escherichia coli (UPEC) infections are common and when they disseminate can be of high morbidity.

Methods: We studied the effects of UPEC infection using single cell RNA sequencing (scRNAseq) in zebrafish. Bulk RNA sequencing has historically been used to evaluate gene expression patterns, but scRNAseq allows gene expression to be evaluated at the single cell level and is optimal for evaluating heterogeneity within cell types and rare cell types. Zebrafish cohorts were injected with either saline or UPEC, and scRNAseq and canonical pathway analyses were performed.

Results: Canonical pathway analysis of scRNAseq data provided key information regarding innate immune pathways in the cells determined to be thymus cells, ionocytes, macrophages/monocytes, and pronephros cells. Pathways activated in thymus cells included interleukin 6 (IL-6) signaling and production of reactive oxygen species. Fc receptor-mediated phagocytosis was a leading canonical pathway in the pronephros and macrophages. Genes that were downregulated in UPEC vs saline exposed embryos involved the cellular response to the Gram-negative endotoxin lipopolysaccharide (LPS) and included Forkhead Box O1a (Foxo1a), Tribbles Pseudokinase 3 (Trib3), Arginase 2 (Arg2) and Polo Like Kinase 3 (Plk3).

Conclusions: Because 4-day post fertilization zebrafish embryos only have innate immune systems, the scRNAseq provides insights into pathways and genes that cell types utilize in the bacterial response. Based on our analysis, we have identified genes and pathways that might serve as genetic targets for treatment and further investigation in UPEC infections at the single cell level.

Background: Poorly ventilated enclosed spaces pose a risk for airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. Limited information is available on ventilation in motor vehicles under differing driving conditions.

Methods: We conducted carbon dioxide measurements to assess ventilation in motor vehicles under varying driving conditions with 2 to 3 vehicle occupants. During routine driving, carbon dioxide produced by the breathing of vehicle occupants was measured inside 5 cars and a van under a variety of driving conditions with or without the ventilation fan on and with windows open or closed. Carbon dioxide readings above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation.

Results: Carbon dioxide levels remained below 800 ppm in all vehicles if the ventilation fan was on and/or the windows were open while parked or during city or highway driving. With the ventilation system set on non-recirculation mode, carbon dioxide levels rose above 800 ppm in all vehicles when the fan was off and the windows were closed while parked and during city driving, and in 2 of the 6 vehicles during highway driving. With the ventilation system set on recirculation mode, carbon dioxide rose above 800 ppm within 10 minutes in all vehicles tested.

Conclusion: Carbon dioxide measurements could provide a practical and rapid method to assess ventilation in motor vehicles. Simple measures such as opening windows, turning on the fan, and avoiding the recirculation mode greatly improve ventilation.

Background: In this work, we carried out a cross-sectional study examining HIV-1 and HCV free virus concentrations in blood and cerebrospinal fluid (CSF) to determine whether HIV-1 enters the central nervous system (CNS) passively as virus particles or in the context of migrating infected cells. If virions migrate freely across the blood-cerebrospinal fluid barrier (BCSFB) or the blood-brain barrier (BBB) then HCV and HIV-1 would be detectable in the CSF at proportions similar to that in the blood. Alternatively, virus entry as an infected cell would favor selective entry of HIV-1.

Methods: We measured HIV-1 and HCV viral loads in the CSF and blood plasma of 4 co-infected participants who were not on antiviral regimens for either infection. We also generated HIV-1 env sequences and performed phylogenetic analyses to determine whether HIV-1 populations in the CSF of these participants were being maintained by local replication.

Results: While CSF samples taken from all participants had detectable levels of HIV-1, HCV was not detectable in any of the CSF samples despite participants having HCV concentrations in their blood plasma, which exceeded that of HIV-1. Further, there was no evidence of compartmentalized HIV-1 replication in the CNS (Supplementary Figure 1). These results are consistent with a model where HIV-1 particles cross the BBB or the BCSFB within infected cells. In this scenario, we would expect HIV-1 to reach the CSF more readily because the blood contains a much greater number of HIV-infected cells than HCV-infected cells.

Conclusions: HCV entry into the CSF is restricted, indicating that virions do not freely migrate across these barriers and supporting the concept that HIV-1 is transported across the BCSFB and/or BBB by the migration of HIV-infected cells as part of an inflammatory response or normal surveillance.

Background: Inadequate ventilation may contribute to the high risk for household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: We evaluated the effectiveness of several interventions recommended to improve ventilation in households. In 7 residential homes, carbon dioxide monitoring was conducted to assess ventilation in occupied open areas such as family rooms and in bedrooms and/or offices. Carbon dioxide levels above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation for the number of people present. In 1 of the 7 homes, various interventions to improve ventilation or to filter air were assessed in a kitchen area by measuring clearance of aerosol particles produced using an aerosol-based spray system and carbon dioxide generated by cooking with a gas stove.

Results: Carbon dioxide levels rose above 800 ppm in bedrooms and offices with 2 occupants when windows and doors were closed and in open areas during gatherings of 5 to 10 people; carbon dioxide levels decreased when windows or doors were opened. Clearance of carbon dioxide and aerosol particles significantly increased with interventions including running fans, operating portable air cleaners, and opening windows, particularly when there was a noticeable breeze or when a window fan was used to blow contaminated air outside.

Conclusion: In households, several measures to improve ventilation or air filtration were effective in reducing carbon dioxide accumulation or enhancing clearance of carbon dioxide and aerosol particles. Studies are needed to determine if interventions to improve ventilation can reduce the risk for airborne transmission of SARS-CoV-2 in households.

Introduction: Neutralizing antibodies have been shown to develop rapidly following SARS-CoV-2 infection, specifically against spike (S) protein, where cytokine release and production is understood to drive the humoral immune response during acute infection. Thus, we evaluated the quantity and function of antibodies across disease severities and analyzed the associated inflammatory and coagulation pathways to identify acute markers that correlate with antibody response following infection.

Methods: Blood samples were collected from patients at time of diagnostic SARS-CoV-2 PCR testing between March 2020-November 2020. Plasma samples were analyzed using the MesoScale Discovery (MSD) Platform using the COVID-19 Serology Kit and U-Plex 8 analyte multiplex plate to measure anti-alpha and beta coronavirus antibody concentration and ACE2 blocking function, as well as plasma cytokines.

Results: A total of 230 (181 unique patients) samples were analyzed across the 5 COVID-19 disease severities. We found that antibody quantity directly correlated with functional ability to block virus binding to membrane-bound ACE2, where a lower SARS-CoV-2 anti-spike/anti-RBD response corresponded with a lower antibody blocking potential compared to higher antibody response (anti-S1 r = 0.884, P < 0.001; anti-RBD r = 0.75, P < 0.001). Across all the soluble proinflammatory markers we examined, ICAM, IL-1β, IL-4, IL-6, TNFα, and Syndecan showed a statistically significant positive correlation between cytokine or epithelial marker and antibody quantity regardless of COVID-19 disease severity. Analysis of autoantibodies against type 1 interferon was not shown to be statistically significant between disease severity groups.

Conclusion: Previous studies have shown that proinflammatory markers, including IL-6, IL-8, IL-1β, and TNFα, are significant predictors of COVID-19 disease severity, regardless of demographics or comorbidities. Our study demonstrated that not only are these proinflammatory markers, as well as IL-4, ICAM, and Syndecan, correlative of disease severity, they are also correlative of antibody quantity and quality following SARS-CoV-2 exposure.

Candida auris is an emerging, multidrug resistant fungal pathogen that causes considerable morbidity and mortality. First identified in Japan in 2009, it has since been reported in more than 40 countries. C. auris can persist for long periods on different environmental surfaces as well as the skin. Clinical isolates are typically resistant to commonly prescribed antifungal drugs. Increasingly recognized as a cause of infections and outbreaks in nosocomial settings, C. auris is difficult to identify using traditional microbiological methods. One of the main reasons for the ongoing spread of C. auris is the multitude of virulence factors it possesses and uses against its human host that enables fungal persistence on the skin surface. Yet, many of the virulence mechanismsare unknown or remain incompletely understood. In this review, we summarize the evolution of virulence of C. auris, offer recommendations for combating this important human pathogen, and suggest directions for further research.

[This corrects the article DOI: 10.20411/pai.v7i1.525.].

Introduction: The rapid diagnosis of tuberculosis recurrence can be challenging due to persistently positive detection of Mycobacterium tuberculosis-specific DNA from sputum and bronchopulmonary samples in the absence of active disease.

Methods: We compared the diagnostic accuracy of the detection of M. tuberculosis-specific DNA by either Xpert (January 2010-June 2018) or Xpert Ultra (July 2018-June 2020) and M. tuberculosis-specific ELISPOT in bronchoalveolar lavage (BAL) samples with M. tuberculosis culture results from sputum or bronchopulmonary samples in patients with suspected recurrence of pulmonary tuberculosis.

Results: Among 44 individuals with previous tuberculosis and a presumptive diagnosis of recurrent pulmonary tuberculosis, 4/44 (9.1%) were diagnosed with recurrent tuberculosis by culture. DNA of M. tuberculosis was detected by Xpert in BAL fluid in 1/4 (25%) individuals with recurrent tuberculosis and in 2/40 (5%) cases with past tuberculosis without recurrence, while BAL-ELISPOT with a cut-off of >4,000 early secretory antigenic target-6-specific or culture filtrate protein-10-specific interferon-γ-producing lymphocytes per 1 million BAL-lymphocytes was positive in 4/4 (100%) individuals with recurrent tuberculosis and in 2/40 (5%) cases of past tuberculosis without recurrence.

Conclusion: M. tuberculosis-specific BAL-ELISPOT is more accurate than BAL-Xpert for the diagnosis of paucibacillary tuberculosis recurrence.

On September 10, 2021, a special tribunal established by the French government launched an inquiry into the activities of former health minister Dr. Agnes Buzyn who was charged with "endangering the lives of others". It is surprising to learn of this accusation and inquiry into the actions of a public health official whose response to the epidemic was, to all appearances, exemplary.