Lisa R. Bishop , Matthew F. Starost , Joseph A. Kovacs
{"title":"CD4, but not Cxcr6, is necessary for control of Pneumocystis murina infection","authors":"Lisa R. Bishop , Matthew F. Starost , Joseph A. Kovacs","doi":"10.1016/j.micinf.2024.105408","DOIUrl":"10.1016/j.micinf.2024.105408","url":null,"abstract":"<div><div>CD4+ T cells are critical to control of <em>Pneumocystis</em> infection, and Cxcr6 has been shown to be upregulated in these cells during infection, but the roles of CD4 and Cxcr6 in this setting are undefined. To explore this, mice deficient in CD4 or Cxcr6 expression were utilized in a co-housing mouse model that mimics the natural route of <em>Pneumocystis</em> infection. Organism load and anti-<em>Pneumocystis</em> antibodies were assayed over time, and immunohistochemistry, flow cytometry, and quantitative PCR were used to characterize host immune responses during infection. CD4 was found to be necessary for clearance of <em>Pneumocystis murina,</em> though partial control was seen in it's absence; based on ThPOK expression, double negative T cells with T helper cell characteristics may be contributing to this control. Using a Cxcr6 deficient mouse expressing <em>gfp</em>, control of infection in the absence of Cxcr6 was similar to that in heterozygous control mice. It is noteworthy that <em>gfp</em> + cells were seen in the lungs with similar frequencies between the 2 strains. Interferon-ɣ and chemokine/ligands Cxcr3, Cxcl9, and Cxcl10 increased during <em>P. murina</em> infection in all models. Thus, CD4, but not Cxcr6, is needed for clearance of <em>P. murina</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105408"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056050","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":"S100A12 inhibits Streptococcus pneumoniae and aids in wound healing of corneal epithelial cells both in vitro and in vivo","authors":"Priyasha Mishra , Sanjay Ch , Abhijit Ghosh , Srijita Kundu , Riddhi Agarwal , Bharathi Bhogapurapu , Swati Biswas , Sanhita Roy","doi":"10.1016/j.micinf.2024.105421","DOIUrl":"10.1016/j.micinf.2024.105421","url":null,"abstract":"<div><div><em>Streptococcus pneumoniae</em>, a leading cause of corneal infections worldwide, are extremely aggressive despite antibiotic sensitivity and exhibit increased resistance towards antibiotics. Antimicrobial peptides are often considered as potent alternatives against antibiotic resistance and here we have investigated the possible roles of S100A12, a host defense peptide, in wound healing and <em>S. pneumoniae</em> infection. S100A12 significantly inhibited growth of <em>S. pneumoniae</em> by disruption of membrane integrity along with increased generation of reactive oxygen species. Additionally, S100A12 accelerated cell migration and wound closure in human corneal epithelial cells and in a murine corneal wound model by activation of EGFR and MAPK signaling pathways.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105421"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154544","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}
Varpu Rinne , Kirsi Gröndahl-Yli-Hannuksela , Ruth Fair-Mäkelä , Marko Salmi , Pia Rantakari , Tapio Lönnberg , Jukka Alinikula , Annukka Pietikäinen , Jukka Hytönen
{"title":"Single-cell transcriptome analysis of the early immune response in the lymph nodes of Borrelia burgdorferi-infected mice","authors":"Varpu Rinne , Kirsi Gröndahl-Yli-Hannuksela , Ruth Fair-Mäkelä , Marko Salmi , Pia Rantakari , Tapio Lönnberg , Jukka Alinikula , Annukka Pietikäinen , Jukka Hytönen","doi":"10.1016/j.micinf.2024.105424","DOIUrl":"10.1016/j.micinf.2024.105424","url":null,"abstract":"<div><div>Lyme borreliosis is a disease caused by <em>Borrelia burgdorferi</em> sensu lato bacteria. <em>Borrelia burgdorferi</em> is known to induce prolonged extrafollicular immune responses and abnormal germinal centre formation. The infection fails to generate a neutralizing type of immunity, eventually establishing a persistent infection. Here, we performed single-cell RNA sequencing to characterize the immune landscape of lymph node lymphocytes during the early <em>Borrelia burgdorferi</em> infection in a murine model.</div><div>Our results indicate key features of an extrafollicular immune response four days after <em>Borrelia burgdorferi</em> infection, including notable B cell proliferation, immunoglobulin class switching to IgG3 and IgG2b isotypes, plasmablast differentiation, and the presence of extrafollicular B cells identified through immunohistochemistry. Additionally, we found infection-derived upregulation of suppressor of cytokine signalling genes <em>Socs1</em> and <em>Socs3,</em> along with downregulation of genes associated with MHC II antigen presentation in B cells.</div><div>Our results support the central role of B cells in the immune response of a <em>Borrelia burgdorferi</em> infection, and provide cues of mechanisms behind the determination between extrafollicular and germinal centre responses during <em>Borrelia burgdorferi</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105424"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290892","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}
{"title":"Suppressive effects of toll-like receptor 2, toll-like receptor 4, and toll-like receptor 7 on protective responses to Mycobacterium bovis BCG from epithelial cells","authors":"Aarti Singh, Akshita Singh, Shakuntala Surender Kumar Saraswati, Ankush Kumar Rana, Aayushi Singh, Chaitenya Verma, Vishal Sinha, Kanika Kalra, Krishnamurthy Natarajan","doi":"10.1016/j.micinf.2024.105428","DOIUrl":"10.1016/j.micinf.2024.105428","url":null,"abstract":"<div><div>Mycobacteria have several mechanisms for evasion of protective responses mounted by the host. In this study, we unravel yet another mechanism that is mediated by Toll-Like Receptors TLR2, TLR4, and TLR7 in epithelial cells. We show that mycobacterial infection of epithelial cells increases the expression of TLR2, TLR4, and TLR7. Stimulation of either TLR along with mycobacterial infection results in an inhibition of oxidative burst resulting in increased survival of mycobacteria inside epithelial cells. TLR stimulation along with mycobacterial infection also inhibits activation of epithelial cells for T cell responses by differentially regulating the activation of ERK-MAPK and p38-MAPK along with inhibition of co-stimulatory molecule CD86 expression. Furthermore, stimulation of either TLR inhibits the induction of apoptosis and autophagy. Knockdown of either TLR by specific siRNAs reverses the inhibition by ROS and apoptosis by mycobacteria and results in reduced intracellular survival of mycobacteria in a MyD88-dependent manner. These results point towards a negative role for TLR2, TLR4, and TLR7 in regulating protective responses to <em>M. bovis</em> BCG infection in epithelial cells.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105428"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378064","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}
Gulinazi Yesitayi , Qi Wang , Mengmeng Wang , Mierxiati Ainiwan , Kaisaierjiang Kadier , Aliya Aizitiaili , Yitong Ma , Xiang Ma
{"title":"LPS-LBP complex induced endothelial cell pyroptosis in aortic dissection is associated with gut dysbiosis","authors":"Gulinazi Yesitayi , Qi Wang , Mengmeng Wang , Mierxiati Ainiwan , Kaisaierjiang Kadier , Aliya Aizitiaili , Yitong Ma , Xiang Ma","doi":"10.1016/j.micinf.2024.105406","DOIUrl":"10.1016/j.micinf.2024.105406","url":null,"abstract":"<div><div>Acute aortic dissection (AAD) is the most severe traumatic disease affecting the aorta. Pyroptosis-mediated vascular wall inflammation is a crucial trigger for AAD, and the exact mechanism requires further investigation. In this study, our proteomic analysis showed that Lipopolysaccharide (LPS)-binding protein (LBP) was significantly upregulated in the plasma and aortic tissue of patients with AAD. Further, 16S rRNA sequencing of stool samples suggested that patients with AAD exhibit gut dysbiosis, which may lead to an impaired intestinal barrier and LPS leakage. By comparing with control mice, we found that LBP, including Pyrin Domain Containing Protein3 (NLRP3), the CARD-containing adapter apoptosis-associated speck-like protein (ASC), and Cleaved caspase-1, were upregulated in the AAD aorta, whereas gut intestinal barrier-related proteins were downregulated. Moreover, treated with LBPK95A (an LBP inhibitor) attenuated the incidence of AAD, the expression levels of pyroptosis-related factors, and the extent of vascular pathological changes compared to those in AAD mice. In addition, LPS and LBP treatment of human umbilical vein endothelial cells (HUVECs) activated TLR4 signaling and intracellular reactive oxygen species (ROS) production, which stimulated NLRP3 inflammasome formation and mediated pyroptosis in endothelial cells. Our findings showed that gut dysbiosis mediates pyroptosis by the LPS-LBP complex, thus providing new insights into developing AAD.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105406"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017967","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}
Yazdan Samieipour , Marian Wiegand , Elena M. Willner , Dieter Hoffmann , Kamyar Shameli , Ulrike Protzer , Hassan Moeini
{"title":"Replication-deficient Sendai virus expressing human norovirus capsid protein elicits robust NoV-specific antibody and T-cell responses in mice","authors":"Yazdan Samieipour , Marian Wiegand , Elena M. Willner , Dieter Hoffmann , Kamyar Shameli , Ulrike Protzer , Hassan Moeini","doi":"10.1016/j.micinf.2024.105412","DOIUrl":"10.1016/j.micinf.2024.105412","url":null,"abstract":"<div><div>Human norovirus (HuNoV) is a major global cause of acute gastroenteritis, with vaccine development facing several challenges. Despite years of research, there are currently no licensed vaccines available for controlling HuNoVs. Here, we describe the construction and testing of a replication-deficient Sendai virus (SeV) vector as a potential vaccine candidate against the HuNoV GII.4 genotype. SeV was chosen as the vaccine backbone due to its non-pathogenic nature in humans, its capability for long-term antigen expression in mammalian cells, and its suitability for mucosal administration. By inserting the HuNoV GII.4 capsid gene, VP1, into the SeV genome, we generated a replication-deficient SeV (SeV/dP.VP1) vector. The resultant SeV/dP.VP1 virus were observed to successfully express the inserted NoV VP1 gene upon infection. Inoculating the vaccine into wild-type mice elicited NoV-specific IgG antibodies, along with INF-γ and IL-2-producing T cells, through both intranasal (i.n.) and intramuscular (i.m.) immunization. Furthermore, a significant level of NoV-specific IgA was detected in lung homogenates after i.n. immunization, particularly using a high dose of the viral vector. Additionally, a synergistic effect was observed with heterologous prime-boost regimens using SeV/dP.VP1 and MVA.VP1 vectors, indicating the potential for more robust immune responses when the vaccine design is optimized. Our study demonstrates the potential of a SeV vaccine candidate in eliciting a broad immune response and lays the foundation for further exploration of the SeV vector platform's potential as a HuNoV vaccine. Additionally, the results emphasize the importance of vaccine dosage and administration route, highlighting the need for tailored immunization strategies.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105412"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140526","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}
Julia Avian Vassalakis , Denise Harumi Silva Yamashita , Leonardo Moura Midon , Bruno Cogliati , Marcos Bryan Heinemann , Thaís Akemi Amamura , Lourdes Isaac
{"title":"Murine C3 of the complement system affects infection by Leptospira interrogans","authors":"Julia Avian Vassalakis , Denise Harumi Silva Yamashita , Leonardo Moura Midon , Bruno Cogliati , Marcos Bryan Heinemann , Thaís Akemi Amamura , Lourdes Isaac","doi":"10.1016/j.micinf.2024.105413","DOIUrl":"10.1016/j.micinf.2024.105413","url":null,"abstract":"<div><div>Leptospirosis is an infectious neglected disease estimated to affect more than one million people worldwide each year. The Complement System plays a vital role in eliminating infectious agents. However, its precise role in leptospirosis remains to be fully understood. We investigated the importance of C3 in <em>L. interrogans</em> serovar Kennewicki strain Pomona Fromm (LPF) infection. Lack of C3 leads to decreased leukocyte number, impaired inflammatory response and failure to eliminate bacteria during the early stages of infection, which may cause interstitial nephritis later. These findings could be explained, at least in part, by the lower presence of local opsonins. Furthermore, antibody production against <em>Leptospira</em> was compromised in the absence of C3, highlighting the importance of CR2 in B lymphocyte proliferation and the adjuvant role of C3d in humoral immunity. Leptospires can be eliminated through the urine, and according to our study, the lack of C3 delays the elimination of LPF through urine during the early stages of the infection. These results strongly suggest the crucial role of C3 protein in orchestrating an appropriate inflammatory response against LPF infection and in effectively eliminating the bacteria from the body during the acute phase of leptospirosis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105413"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290891","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":"Detection of various DNA and RNA viruses in bats in Yamaguchi Prefecture, Japan","authors":"Miyuka Nishizato , Urara Imai , Chisato Shigenaga , Miho Obata , Saki Mitsunaga , Marla Anggita , Samuel Nyampong , Shelly Wulandari , Weiyin Hu , Kazuki Kiuno , Lydia Mali Langata , Hiroyuki Imai , Masashi Sakurai , Tetsuya Yanagida , Ai Takano , Takashi Murakami , Chang-Gi Jeong , Jae-Ku Oem , Daisuke Hayasaka , Hiroshi Shimoda","doi":"10.1016/j.micinf.2024.105425","DOIUrl":"10.1016/j.micinf.2024.105425","url":null,"abstract":"<div><div>Bats are important natural hosts of various zoonotic viruses, including Ebola virus, Lyssa virus, and severe acute respiratory syndrome coronavirus (SARS-CoV). Although investigation of bats is valuable for predicting emerging infectious diseases from these animals, few surveys of bat-derived viruses have been conducted in Japan. In the present study, samples were collected from a total of 132 bats of 4 different species from 4 different locations within Yamaguchi Prefecture; these sample were employed for comprehensive detection of bat-derived viruses by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR using primers universal for each of 4 different viral classes. As a result of PCR and RT-PCR, various herpesviruses, astroviruses, coronaviruses, and adenoviruses were identified from a total of 80 bats. The detected herpesviruses belong to the <em>Betaherpesvirinae</em> or <em>Gammaherpesvirinae</em> subfamily, the detected adenoviruses to the genus <em>Mastadenovirus</em>, the detected astroviruses to the genus <em>Mamastrovirus</em>; and the detected coronaviruses belong to the genus <em>Alphacoronavirus</em>. The detected sequences of 12 strains of 4 families showed 100 % amino acid identity with viruses previously detected either in China or South Korea. These findings expand our understanding of viruses carried by bats, and provide insights into the nature of bat-derived viruses in Japan.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105425"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349787","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}
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}