Explore the vast range of titles available.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry starts with membrane attachment and ends with spike (S) protein—catalyzed membrane fusion depending on two cleavage steps, namely, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time three-dimensional single-virion tracking, we show that fusion and genome penetration require virion exposure to an acidic milieu of pH 6.2 to 6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2-overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2-expressing cells in the acidic milieu of the nasal cavity.

Background Nocardia , a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica ( N. farcinica ) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue. Methods BALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 10 7 CFU through three infection routes, after which brain tissue was harvested. Results Intraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes. Conclusion The study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.

Background Aeromonas schubertii , an emerging pathogen primarily recognized in humans, shrimps, and other mammals, is increasingly implicated in aquatic animal diseases. Despite its growing prevalence, reports of its involvement in fish diseases are limited. This study investigates a natural outbreak of A. schubertii associated with high mortality in cultured Asian seabass ( Lates calcarifer ) in Thailand and suggest its potential pathogenicity in cultured fish species. Results To investigate the cause of mortality in Asian seabass at a commercial farm in central Thailand, two A. schubertii isolates—CHULA2021a and CHULA2021b—were recovered from moribund and dead juvenile fish. Naturally infected fish exhibited lethargy and slow swimming behavior, without any visible external lesions. In experimentally infected fish, clinical signs developed within 96 h post-exposure and included nodular lesion, and severe necrosis in the spleen, kidney, and liver. Histological examination revealed extensive infiltration of inflammatory cells, multifocal necrosis, marked hepatic damage, and occasional granuloma-like formations. Immunohistochemistry detected A. schubertii antigens predominantly in gill epithelium and phagocytic cells with the strongest signals observed in the head kidney. Survival analysis demonstrated significantly higher mortality in both immersion (87%) and injection (90%) groups compared to controls. Genomic analysis revealed a 4.2 Mb genome with 61% GC content. Phylogenetic analysis grouped A. schubertii with related Aeromonas species and highlighted distinct genetic features. Most identified virulence genes were related to adherence, particularly flagellar function, followed by a substantial number associated with secretion systems, predominantly type III and type VI. Conclusions This study reports the presence of A. schubertii in Asian seabass and its association with significant mortality during a natural outbreak. The integration of experimental infection data, histopathology, and immunohistochemistry contributes to a comprehensive understanding of its pathogenicity and supports the development of effective control measures. Additionally, genome analysis and identification of virulence genes providing molecular insights into potential virulence mechanisms. These findings enhance our understanding of the organism’s pathogenic mechanisms and provide insights for future diagnostics and disease management strategies.

Despite being a bacterial pathogen with devastating consequences, 's pathogenesis is not fully understood. The aim of the present study was to elucidate if different inoculation routes (intraperitoneal - i.p - injection and bath challenge - known to induce mortality) can induce tenacibaculosis (i.e., using the same inoculum), as well as evaluate the short-term immune response of European sea bass ( ). Additionally, the host response against i.p. injection of extracellular products (ECPs) was also studied. Fish were i.p. challenged with 5.5 × 10 CFU mL of cells with or without ECPs (BECPs and BWO, respectively), ECPs alone or marine broth (mock). Another group of fish was bath-challenged with 5.5 × 10 CFU mL to confirm the virulence of the bacterial inoculum. Undisturbed specimens were used as controls. The severity of both challenges was determined by following percentage survival. Blood, liver and head-kidney samples were collected at 0, 3, 6, 24 and 48 h post-challenge for assessing immune parameters, oxidative stress and gene expression. Total and differential peritoneal cell counts were performed. The presence of viable bacteria in the blood and peritoneal cavity was studied. Symptoms of tenacibaculosis, such as skin/fin abrasions, were only observed in the bath-challenged fish, where 0% survival was recorded, whereas 100% survival was observed after i.p. injection of the same bacterial inoculum. An increase in total leukocyte numbers in the peritoneal cavity was observed 3 h post-injection of BECPs when compared to the other treatments. Blood total leukocytes, lymphocytes, and thrombocyte numbers dropped after the challenge, mainly in fish challenged with BECPs. At 48 h post-challenge, bactericidal activity in the plasma increased in fish injected with bacteria (with and without ECPs). The same tendency was seen for some of the oxidative stress parameters. The increased expression of , in fish challenged with ECPs and BECPs suggests a more exacerbated pro-inflammatory response in the head-kidney against these inocula. The infection trial and the observed immune responses showed that the infection route is a determinant factor regarding -induced pathogenesis in European sea bass.

Campylobacter fetus subspecies fetus was identified in the peritoneal dialysate of a 42-year-old patient undergoing continuous ambulatory peritoneal dialysis (CAPD). The patient initially received intraperitoneal ceftazidime and cefazolin sodium for 10 days, which led to significant symptom relief. However, bacterial cultures of the peritoneal dialysate remained positive. Further history revealed that the patient frequently dined at her father’s home, where turtles were kept, suggesting that turtle feces might be the source of infection. Subsequently, the treatment regimen was changed to oral amoxicillin-clavulanate potassium for 3 days, and the patient was advised to avoid contact with turtles. One week after discharge, follow-up cultures of the peritoneal fluid showed no bacterial growth. This case, combined with a review of the literature, provides valuable insights into the diagnosis and management of this rare infection. Clinical trial number Not applicable.

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis.

Toxoplasma gondii is a highly successful parasite capable of infecting all warm-blooded animals. The natural way of infection in intermediate hosts is the oral ingestion of parasite-contaminated water or food. In murine experimental models, oral infection ( p.o. ) of mice with T. gondii is applied to investigate mucosal and peripheral immune cell dynamics, whereas intraperitoneal infection ( i.p. ) is frequently used to study peripheral inflammation as well as immune cell – neuronal interaction in the central nervous system (CNS). However, the two infection routes have not yet been systematically compared along the course of infection. Here, C57BL/6 mice were infected p.o. or i.p. with a low dose of T. gondii cysts, and the acute and chronic stages of infection were compared. A more severe course of infection was detected following i.p. challenge, characterized by an increased weight loss and marked expression of proinflammatory cytokines particularly in the CNS during the chronic stage. The elevated proinflammatory cytokine expression in the ileum was more prominent after p.o. challenge that continued following the acute phase in both i.p. or p.o. infected mice. This resulted in sustained microbial dysbiosis, especially after p.o. challenge, highlighted by increased abundance of pathobionts from the phyla proteobacteria and a reduction of beneficial commensal species. Further, we revealed that in the CNS of i.p. infected mice CD4 and CD8 T cells displayed higher IFNγ production in the chronic stage. This corresponded with an increased expression of C1q and CD68 in the CNS and reduced expression of genes involved in neuronal signal transmission. Neuroinflammation-associated synaptic alterations, especially PSD-95, VGLUT, and EAAT2 expression, were more pronounced in the cortex upon i.p. infection highlighting the profound interplay between peripheral inflammation and CNS homeostasis.

Background Intervertebral disc degeneration (IVDD) is a primary cause of chronic low back pain. Recent evidence suggests a potential association between low-virulence infections, particularly by Cutibacterium acnes , and IVDD. However, the pathways and mechanisms by which this commensal skin bacterium infects intervertebral discs remain poorly understood. Objective The purpose of this study was to determine whether Cutibacterium acnes can enter the intervertebral disc through hematogenous or contiguous routes, and whether injury-induced damage to the annulus fibrosus and IVDD increases susceptibility to infection, using an animal model. Methods To investigate Cutibacterium acnes infection pathways, Sprague-Dawley rats underwent caudal disc annulus fibrosus puncture or remained intact (confirmed by 28-day MRI T2WI). After MRI, hematogenous and contiguous infections were modeled by daily Cutibacterium acnes injections for 7 days. Tail-vein injections were given in Groups A (intact discs) and C (punctured discs) to simulate hematogenous spread, while subcutaneous injections were given in Groups B (intact discs) and D (punctured discs) to simulate contiguous spread. Intervertebral disc samples were taken under very strict aseptic conditions after the intervention. Gram staining and Cutibacterium acnes -specific 16S rDNA PCR were used to confirm the presence of Cutibacterium acnes in these disc specimens cultured under aerobic and anaerobic conditions. The remaining segment was subjected to histological evaluation (H&E staining). Results Intervertebral disc puncture successfully induced IVDD, as evidenced by MRI and histology. Punctured discs exhibited significantly higher susceptibility to Cutibacterium acnes infection via both hematogenous (Group C: 17.5% vs. Group A: 0%; P =  0.012) and contiguous spread (Group D: 20% vs. Group B: 0%; P = 0.005), as confirmed by anaerobic culture. No bacteria were cultured in an aerobic environment, and the PBS group. Conclusions Annulus fibrosus injury and IVDD significantly increase the risk of intervertebral disc Cutibacterium acnes infection through hematogenous and contiguous spread pathways.

The threat of severe fever with thrombocytopenia syndrome (SFTS) to public health has been increasing due to the rapid spread of the ticks that carry the causative viral agent. The SFTS virus (SFTSV) was first identified in China and subsequently detected in neighboring countries, including South Korea, Japan, and Vietnam. In addition to the tick-mediated infection, human-to-human transmission has been recently reported with a high mortality rate; however, differential study of the pathogen has been limited by the route of infection. In this study, we investigated the pathogenic potential of SFTSV based on the infection route in aged ferrets, which show clinical signs similar to that of human infections. Ferrets inoculated with SFTSV via the intramuscular and subcutaneous routes show clinical signs comparable to those of severe human infections, with a mortality rate of 100%. Contrastingly, intravascularly infected ferrets exhibit a comparatively lower mortality rate of 25%, although their early clinical signs are similar to those observed following infection via the other routes. These results indicate that the infection route could influence the onset of SFTS symptoms and the pathogenicity of SFTSV. Thus, infection route should be considered in future studies on the pathogenesis of SFTSV infection.

Male rodents are almost exclusively used for experimental maintenance of filarial nematodes because they have higher susceptibility to parasitism than female rodents. This study investigates the effects that rodent host sex has on the worm transcriptome for subcutaneous (SQ) infections and intraperitoneal (IP) infections. Significantly more adult worms were recovered from IP-infected gerbils (median = 78 worms/infected animal) relative to SQ-infected gerbils (median = 2 worms/infected animal). Microfilaria production in male gerbils infected via the SQ route (mean = 6.62 microfilariae (mf)/20 µL, median = 5.65 mf/20 µL) was significantly greater than in female gerbils (mean = 0.43 mf/20 µL, median = 0 mf/20 µL). Male gerbils were also significantly more susceptible to SQ infection than females with a prevalence of 90% (n = 20) in males vs 27% (n = 29) in female gerbils. There was no significant difference in the number of adult worms recovered between male and female gerbils for either infection route. No statistically significant gene expression differences were observed in comparisons of worms of the same life stage/sex from male and female gerbils. In subcutaneously infected gerbils, the identification of differentially expressed genes was likely precluded by the markedly different transcript profiles between replicates. However, the transcriptional profiles for IP-infected gerbils were homogenous suggesting that the host sex does not alter nematode gene expression in the life stages examined from the IP model. The lack of impact of host sex on the transcriptome of worms isolated from IP-infected gerbils reinforces the use of male gerbils as the primary rearing host for these parasites. Genome annotation of B. pahangi is reported as it was required for this differential expression analysis.