Jaehoo Lee, Yongxin Jin, Weihui Wu, Yeji Lee, Un-Hwan Ha
{"title":"Pseudomonas aeruginosa-derived DnaJ induces TLR2 expression through TLR10-mediated activation of the PI3K-SGK1 pathway in macrophages.","authors":"Jaehoo Lee, Yongxin Jin, Weihui Wu, Yeji Lee, Un-Hwan Ha","doi":"10.1016/j.micinf.2025.105481","DOIUrl":"https://doi.org/10.1016/j.micinf.2025.105481","url":null,"abstract":"<p><p>TLR2 is a key component of the innate immune system, responsible for recognizing Gram-positive bacterial components and initiating inflammatory signaling cascades that activate defense responses. However, little is known about the regulatory effects of Pseudomonas aeruginosa (P. aeruginosa) on TLR2 expression. In this study, we investigated the potential link between P. aeruginosa-derived DnaJ and TLR2 expression in macrophages, as well as the activation of downstream signaling pathways. Our findings revealed that DnaJ significantly induced TLR2 expression in a dose- and time-dependent manner, predominantly affecting TLR2 with minimal impact on other TLRs, such as TLR4 and TLR5, which detect bacterial PAMPs. The DnaJ-mediated TLR2 induction was driven by activation of the PI3K-SGK1 signaling pathway, with TLR10 playing a crucial role in facilitating these effects. This increase in TLR2 expression led to enhanced production of inflammatory cytokines in response to secondary Staphylococcus aureus infections, indicating a role in boosting host defense mechanisms. In conclusion, these findings suggest that P. aeruginosa-derived DnaJ promotes TLR2 expression via TLR10-mediated activation of the PI3K-SGK1 pathway, thereby enhancing host immune responses against Gram-positive bacterial infections.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105481"},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunostimulatory effects of Hsp70 fragments-modified DCs: A computational and experimental study in HIV vaccine design.","authors":"Elahe Akbari, Alireza Milani, Parisa Moradi Pordanjani, Masoud Seyedinkhorasani, Elnaz Agi, Azam Bolhassani","doi":"10.1016/j.micinf.2025.105480","DOIUrl":"10.1016/j.micinf.2025.105480","url":null,"abstract":"<p><strong>Background: </strong>Dendritic cells (DCs) loaded with HIV-1 antigens have been explored as a promising therapeutic approach to overcome HIV-1 infection. Heat shock proteins (Hsps) can improve cross-presentation of linked antigens by DCs. Our aim was a comprehensive in silico, in vitro, and in vivo evaluation of fusion proteins comprising the N- and C-terminal regions of Hsp70 (i.e., NT-Hsp70 and CT-Hsp70) as an adjuvant linked to HIV-1 Nef antigen in development of DCs-based vaccine candidates.</p><p><strong>Methods: </strong>Computational analyses of the NT-Hsp70-Nef and CT-Hsp70-Nef fusion constructs were performed, and their structural features and docking ability with toll-like or endocytic receptors were evaluated. The effectiveness of DCs loaded with the fusion proteins in eliciting immunity was assessed in mice. Cytokine secretion levels from splenocytes exposed to single-cycle replicable (SCR) HIV-1 were also measured in vitro.</p><p><strong>Results: </strong>The DCs pulsed with the fusion constructs induced robust cellular and humoral immune responses in mice and infected splenocytes. The CT-Hsp70 region showed better docking scores with immune receptors and superior adjuvanticity for inducing Nef-specific immune responses (Th1 and CTL activity) compared to the NT-Hsp70 region in DC-based immunization.</p><p><strong>Conclusions: </strong>The CT-Hsp70-Nef protein demonstrated promising results in both computational and experimental analyses compared to the NT-Hsp70-Nef protein.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105480"},"PeriodicalIF":2.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endogenous retroviruses in neurodevelopmental, psychotic and cognitive disorders.","authors":"Urs Meyer, Iris Katharina Penner","doi":"10.1016/j.micinf.2025.105479","DOIUrl":"10.1016/j.micinf.2025.105479","url":null,"abstract":"<p><p>Endogenous retroviruses (ERVs) are inherited retroviral genomic elements that integrated into the mammalian genome through germline infections and insertions during evolution. Human ERVs (HERVs) comprise approximately 8 % of the human genome and are increasingly recognized to be involved in the etiology and pathophysiology of numerous brain disorders. In this narrative review, we summarize the existing evidence linking abnormal HERV expression to neurodevelopmental and psychosis-related disorders and discuss how these retroviral elements may contribute to the heterogeneity in clinical outcomes. We also review the findings suggesting that aberrant HERV expression contribute to late-onset cognitive disorders with neurodegenerative components, such as Alzheimer's disease (AD) and other forms of dementia. The evidence implicating abnormal HERV expression in neurodevelopmental, psychotic, and cognitive disorders is manifold and stems from diverse research fields, including human post-mortem brain studies, serological investigations, gene expression analyses, and clinical trials with HERV-specific pharmacological compounds. The recent establishment and use of animal models offer a complementary experimental platform that will help establish causal relationships and identify specific disease pathways affected by abnormal HERV expression. Yet, significant gaps persist in understanding the role of HERVs in neurodevelopmental, psychotic, and cognitive disorders, particularly concerning the specificity and stability of abnormal HERV expression in these conditions. Addressing these questions appears crucial for optimizing the potential benefits of therapeutic interventions aimed at targeting abnormal HERV expression across the broad spectrum of HERV-associated disorders of the central nervous system.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105479"},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vita Petrone, Rossana Scutari, Vincenzo Malagnino, Lorenzo Piermatteo, Mirko Compagno, Romina Salpini, Martina Giudice, Marialaura Fanelli, Elisabetta Teti, Marco Iannetta, Antonella Minutolo, Maria Mercedes Santoro, Valentina Svicher, Paola Sinibaldi Vallebona, Massimo Andreoni, Emanuela Balestrieri, Loredana Sarmati, Francesca Ceccherini-Silberstein, Sandro Grelli, Claudia Matteucci
{"title":"The transactivation of human endogenous retroviruses is associated with HIV-1 reservoir, lymphocyte activation and low CD4 count in virologically suppressed PLWH.","authors":"Vita Petrone, Rossana Scutari, Vincenzo Malagnino, Lorenzo Piermatteo, Mirko Compagno, Romina Salpini, Martina Giudice, Marialaura Fanelli, Elisabetta Teti, Marco Iannetta, Antonella Minutolo, Maria Mercedes Santoro, Valentina Svicher, Paola Sinibaldi Vallebona, Massimo Andreoni, Emanuela Balestrieri, Loredana Sarmati, Francesca Ceccherini-Silberstein, Sandro Grelli, Claudia Matteucci","doi":"10.1016/j.micinf.2025.105478","DOIUrl":"10.1016/j.micinf.2025.105478","url":null,"abstract":"<p><p>In the context of long-term therapy in virologically suppressed people living with HIV-1 (PLWH), the identification of new biomarkers associated with immuno-virological discordance, and the risk of disease progression is needed. Herein we investigated HERVs expression in association with immuno-virological discordance parameters for the identification of novel markers for the clinical monitoring of virologically suppressed PLWH. It is known the human endogenous retroviruses (HERVs), relics of ancestral exogenous retroviral infections comprising 8 % of human genome, could be reactivated by exogenous viruses including HIV-1. The study included 31 virologically suppressed PLWH and 10 healthy donors; blood HIV-DNA levels and residual plasma viremia were quantified by droplet digital-PCR, the expression of HERVs by RT-Real time PCR, and immunophenotyping by flow cytometry. The results revealed a dynamic association of HERVs with several virological and immunological parameters such as the HIV-1 reservoir, CD4 cell count, CD4 nadir and with CD8 and CD19 lymphocyte activation. In an era of searching innovative biomarkers for people living with HIV-1, the interconnection of HERVs with the HIV-1 reservoir and lymphocyte activation opens to further investigation on HERVs role in persistent immune activation in virologically suppressed PLWH, proposing them as potential new markers for clinical monitoring.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105478"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rabia Ladjouzi, Bernard Taminiau, Georges Daube, Anca Lucau-Danila, Djamel Drider
{"title":"The efficacy of the bacteriocinogenic Enterococcus faecalis 14 in the control of induced necrotic enteritis in broilers.","authors":"Rabia Ladjouzi, Bernard Taminiau, Georges Daube, Anca Lucau-Danila, Djamel Drider","doi":"10.1016/j.micinf.2025.105477","DOIUrl":"https://doi.org/10.1016/j.micinf.2025.105477","url":null,"abstract":"<p><strong>Purpose: </strong>To demonstrate the efficacy of the bacteriocinogenic Enterococcus faecalis 14 (E. faecalis 14) in the control of induced necrotic enteritis (NE) in broilers.</p><p><strong>Methods: </strong>Six groups of 504 broilers consisting of an infected untreated control (IUC) group, an infected and amoxicillin treated control (ITC) group, and groups receiving prophylactically (2 groups) or therapeutically (2 groups) E. faecalis 14 or its Δbac mutant were used. All groups were challenged with Clostridium perfringens 56 to induce NE. To predispose the boilers to develop subclinical NE, a high protein grower diet containing 15% fishmeal and a coccidial inoculum were administered.</p><p><strong>Results: </strong>NE lesions were observed on D26 in all groups except ITC and those receiving prophylactically and therapeutically E. faecalis 14. On D27, only ITC and the group prophylactically treated with E. faecalis 14 (T03 T03) were without lesions. Average body weight and daily weight gain remained lower in the treated groups compared to the ITC group, but there was a clear improvement in the period between D21 to D27, especially in the group prophylactically treated with E. faecalis 14. Specifically, the daily weight gain (DWG) in this period for group T03, was second highest after the group ITC. Metataxonomic analyses showed a positive effect of E. faecalis 14 in maintaining the diversity and richness of the intestinal microbiota, in contrast to ITC group and other conditions.</p><p><strong>Conclusions: </strong>The results of this in vivo study demonstrated the efficacy of the prophylactic administration of the bacteriocinogenic E. faecalis 14 in preventing of the NE lesions caused by C. perfringens.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105477"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thais A Amamura, Daniella Dos S Courrol, Angela S Barbosa, Ildefonso A Silva-Junior, Tiago F da Silva, Leonardo M Midon, Mario C Cruz, Marcos B Heinemann, Rosa M Chura-Chambi, Ligia Morganti, Lourdes Isaac
{"title":"Proteolytic activity of secreted proteases from pathogenic leptospires and effects on phagocytosis by murine macrophages.","authors":"Thais A Amamura, Daniella Dos S Courrol, Angela S Barbosa, Ildefonso A Silva-Junior, Tiago F da Silva, Leonardo M Midon, Mario C Cruz, Marcos B Heinemann, Rosa M Chura-Chambi, Ligia Morganti, Lourdes Isaac","doi":"10.1016/j.micinf.2025.105469","DOIUrl":"https://doi.org/10.1016/j.micinf.2025.105469","url":null,"abstract":"<p><p>Leptospirosis is a zoonosis caused by spirochete Leptospira. Pathogenic leptospires evade the Complement System, enabling their survival upon contact with normal human serum in vitro. In a previous study, we demonstrated that proteases secreted by pathogenic leptospires cleave several Complement proteins, including C3 and the opsonins C3b and iC3b. We hypothesize that these Leptospira proteases, such as thermolysin and leptolysin, may decrease the phagocytic activity of murine peritoneal macrophages. We observed decreased amounts of CR3 and CR4 using flow cytometry when these cells were treated with supernatant from the culture of pathogenic leptospires (SPL) for 24 h. Through confocal microscopy, we observed a reduction in TLR2, CD11b, and CD206 (mannose receptor) levels when these cells were treated with SPL or recombinant thermolysin for 24 h. Furthermore, opsonins such as C3b/iC3b deposited on the surface of pathogenic leptospires were clearly degraded in the presence of recombinant thermolysin or recombinant leptolysin. Consequently, when opsonized bacteria and macrophages were previously incubated with these proteases, phagocytic activity was diminished. These observations lead us to suggest that proteases secreted by pathogenic leptospires could degrade opsonins present in normal serum or deposited on the bacterial membrane, as well as cleave or inhibit macrophage surface molecules. Therefore, these proteases could interfere with the recognition and internalization by murine macrophages, favoring the spread of leptospires in the host.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105469"},"PeriodicalIF":2.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bacterial and host factors involved in zoonotic Streptococcal meningitis","authors":"Jiale Ma , Huizhen Wu , Zhe Ma , Zongfu Wu","doi":"10.1016/j.micinf.2024.105335","DOIUrl":"10.1016/j.micinf.2024.105335","url":null,"abstract":"<div><div>Zoonotic streptococci cause several invasive diseases with high mortality rates, especially meningitis. Numerous studies elucidated the meningitis pathogenesis of zoonotic streptococci, some specific to certain bacterial species. In contrast, others are shared among different bacterial species, involving colonization and invasion of mucosal barriers, survival in the bloodstream, breaching the blood–brain and/or blood–cerebrospinal fluid barrier to access the central nervous system, and triggering inflammation of the meninges. This review focuses on the recent advancements in comprehending the molecular and cellular events of five major zoonotic streptococci responsible for causing meningitis in humans or animals, including <em>Streptococcus agalactiae</em>, <em>Streptococcus equi</em> subspecies <em>zooepidemicus</em>, <em>Streptococcus suis</em>, <em>Streptococcus dysgalactiae</em>, and <em>Streptococcus iniae</em>. The underlying mechanism was summarized into four themes, including 1) bacterial survival in blood, 2) brain microvascular endothelial cell adhesion and invasion, 3) penetration of the blood–brain barrier, and 4) activation of the immune system and inflammatory reaction within the brain. This review may contribute to developing therapeutics to prevent or mitigate injury of streptococcal meningitis and improve risk stratification.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 1","pages":"Article 105335"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative genome analysis of Streptococcus suis serotype 5 strains from humans and pigs revealed pathogenic potential of virulent, antimicrobial resistance, and genetic relationship","authors":"Anusak Kerdsin , Rujirat Hatrongjit , Thidathip Wongsurawat , Piroon Jenjaroenpun , Han Zheng , Peechanika Chopjitt , Parichart Boueroy , Nahuel Fittipaldi , Mariela Segura , Marcelo Gottschalk","doi":"10.1016/j.micinf.2023.105273","DOIUrl":"10.1016/j.micinf.2023.105273","url":null,"abstract":"<div><div><em>Streptococcus suis</em> is a causative agent of swine and human infections. Genomic analysis indicated that eight <em>S. suis</em> serotype 5 strains recovered from human patients and pigs carried many virulence-associated genes and markers defining pathogenic pathotypes. The strains were sequence types diverse and clustered within either minimum core genome group 3 (MCG-3) or MCG-7-3. Almost all the serotype 5 strains were non-susceptible to penicillin, ceftriaxone, erythromycin, and levofloxacin. Resistance to tetracycline and clindamycin was observed in all strains. The antimicrobial resistance genes <em>tet(O), tet(O/W/32/O), tet(W)</em>, <em>tet(44)</em>, <em>erm(B), ant(6)-Ia, lsaE</em>, and <em>lnuB</em> were found in these strains. Moderate-to-large numbers of substitutions were observed in three penicillin-binding proteins (PBP)—PBP1A, PBP2B, and PBP2X—in the penicillin-non-susceptible serotype 5 isolates that were involved in β-lactam-non-susceptibility. Comparative genomics between the serotype 5 and 2 strains revealed that only 15 genes absent from the serotype 2 strains were shared by all the serotype 5 strains. However, some additional genes were present only in some of the serotype 5 strains. This study highlighted the pathogenic potential of virulent serotype 5 strains in humans and pigs and the need for increased monitoring of penicillin-non-susceptibility in <em>S. suis</em> serotypes other than for serotype 2.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 1","pages":"Article 105273"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138558348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alba Espí-Malillos , Carla Palacios-Gorba , Inmaculada López-Almela , Pilar Ruiz-García , María Carmen López-Mendoza , Francisco García-Del Portillo , M Graciela Pucciarelli , Juan J. Quereda
{"title":"Kinetic and proteomic studies in milk show distinct patterns among major Listeria monocytogenes clones","authors":"Alba Espí-Malillos , Carla Palacios-Gorba , Inmaculada López-Almela , Pilar Ruiz-García , María Carmen López-Mendoza , Francisco García-Del Portillo , M Graciela Pucciarelli , Juan J. Quereda","doi":"10.1016/j.micinf.2024.105312","DOIUrl":"10.1016/j.micinf.2024.105312","url":null,"abstract":"<div><div><em>Listeria monocytogenes</em>, a contaminant of raw milk, includes hypervirulent clonal complexes (CC) like CC1, CC4, and CC6, highly overrepresented in dairy products when compared to other food types. Whether their higher prevalence in dairy products is the consequence of a growth advantage in this food remains unknown. We examined growth kinetics of five <em>L. monocytogenes</em> isolates (CC1, CC4, CC6, CC9, and CC121) at 37 and 4 °C in ultra-high temperature (UHT) milk and raw milk. At 4 °C, hypovirulent CC9 and CC121 isolates exhibit better growth parameters in UHT milk compared to the hypervirulent CC1, CC4, and CC6 isolates. CC9 isolate in raw milk at 4 °C exhibited the fastest growth and the highest final concentrations. In contrast, hypervirulent isolates (CC1, CC4, and CC6) displayed better growth rates in UHT milk at 37 °C, the mammalian host temperature. Proteomic analysis of representative hyper- (CC1) and hypovirulent (CC9) isolates showed that they respond to milk cues differently with CC-specific traits. Proteins related to metabolism (such as LysA or different phosphotransferase systems), and stress response were upregulated in both isolates during growth in UHT milk. Our results show that there is a <em>Listeria</em> CC-specific and a <em>Listeria</em> CC-common response to the milk environment. These findings shed light on the overrepresentation of hypervirulent <em>L. monocytogenes</em> isolates in dairy products, suggesting that CC1 and CC4 overrepresentation in dairy products made of raw milk may arise from contamination during or after milking at the farm and discard an advantage of hypervirulent isolates in milk products when stored at refrigeration temperatures.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 1","pages":"Article 105312"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}