Manmeet Bhalla, Sydney Herring, Alexsandra Lenhard, Joshua R Wheeler, Fred Aswad, Klaus Klumpp, Justin Rebo, Yan Wang, Kevin Wilhelmsen, Kristen Fortney, Elsa N Bou Ghanem
Streptococcus pneumoniae (pneumococcus) remains a serious cause of pulmonary and systemic infections globally, and host-directed therapies are lacking. The aim of this study was to test the therapeutic efficacy of asapiprant, an inhibitor of prostaglandin D2 signaling, against pneumococcal infection. Treatment of young mice with asapiprant after pulmonary infection with invasive pneumococci significantly reduced systemic spread, disease severity, and host death. Protection was specific against bacterial dissemination from the lung to the blood but had no effect on pulmonary bacterial burden...
April 17, 2024: Infection and Immunity
Jia Mun Chan, Elisa Ramos-Sevillano, Modupeh Betts, Holly U Wilson, Caroline M Weight, Ambrine Houhou-Ousalah, Gabriele Pollara, Jeremy S Brown, Robert S Heyderman
Streptococcus pneumoniae , a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human infection studies. We hypothesized that surface expression of pneumococcal lipoproteins, recognized by the innate immune receptor TLR2, mediates epithelial microinvasion. Mutation of lgt in serotype 4 (TIGR4) and serotype 6B (BHN418) pneumococcal strains abolishes the ability of the mutants to activate TLR2 signaling. Loss of lgt also led to the concomitant decrease in interferon signaling triggered by the bacterium...
April 17, 2024: Infection and Immunity
Kevin C Jennings, Kaitlin E Johnson, Michael A Hayward, Christopher J Kristich, Nita H Salzman
Enterococci are common commensal bacteria that colonize the gastrointestinal tracts of most mammals, including humans. Importantly, these bacteria are one of the leading causes of nosocomial infections. This study examined the role of colonic macrophages in facilitating Enterococcus faecalis infections in mice. We determined that depletion of colonic phagocytes resulted in the reduction of E. faecalis dissemination to the gut-draining mesenteric lymph nodes. Furthermore, we established that trafficking of monocyte-derived CX3CR1-expressing macrophages contributed to E...
April 17, 2024: Infection and Immunity
Xin Feng, Jia-Li Yu, Yi-Fan Sun, Chen-Yan Du, Yao Shen, Lu Zhang, Wei-Zhong Kong, Su Han, Yang Cheng
Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response...
April 16, 2024: Infection and Immunity
Lara Lovelace-Macon, Sarah M Baker, Deirdre Ducken, Sudeshna Seal, Guilhem Rerolle, Diane Tomita, Kelly D Smith, Sandra Schwarz, T Eoin West
Melioidosis is an emerging tropical infection caused by inhalation, inoculation, or ingestion of the flagellated, facultatively intracellular pathogen Burkholderia pseudomallei . The melioidosis case fatality rate is often high, and pneumonia, the most common presentation, doubles the risk of death. The alveolar macrophage is a sentinel pulmonary host defense cell, but the human alveolar macrophage in B. pseudomallei infection has never been studied. The objective of this study was to investigate the host-pathogen interaction of B...
April 15, 2024: Infection and Immunity
Stephen J Billington, Eva U Wieckowski, Mahfuzur R Sarker, Dawn Bueschel, J Glenn Songer, Bruce A McClane
No abstract text is available yet for this article.
April 12, 2024: Infection and Immunity
Katherine R Landwehr, Caitlyn M Granland, Kelly M Martinovich, Naomi M Scott, Elke J Seppanen, Luke Berry, Deborah Strickland, Alma Fulurija, Peter C Richmond, Lea-Ann S Kirkham
Nontypeable Haemophilus influenzae (NTHi) is a major otitis media (OM) pathogen, with colonization a prerequisite for disease development. Most acute OM is in children <5 years old, with recurrent and chronic OM impacting hearing and learning. Therapies to prevent NTHi colonization and/or disease are needed, especially for young children. Respiratory viruses are implicated in driving the development of bacterial OM in children. We have developed an infant mouse model of influenza-driven NTHi OM, as a preclinical tool for the evaluation of safety and efficacy of clinical therapies to prevent NTHi colonization and the development of OM...
April 11, 2024: Infection and Immunity
Andrew S Bray, M Ammar Zafar
Bacterial infections pose a significant global health threat, accounting for an estimated 7.7 million deaths. Hospital outbreaks driven by multi-drug-resistant pathogens, notably Klebsiella pneumoniae ( K. pneumoniae ), are of grave concern. This opportunistic pathogen causes pneumonia, urinary tract infections, and bacteremia, particularly in immunocompromised individuals. The rise of hypervirulent K. pneumoniae adds complexity, as it increasingly infects healthy individuals. Recent epidemiological data suggest that asymptomatic gastrointestinal carriage serves as a reservoir for infections in the same individual and allows for host-to-host transmission via the fecal-oral route...
April 10, 2024: Infection and Immunity
M V Miner, I Rauch
Certain Escherichia coli ( E. coli ) strains are attaching and effacing (A/E) lesion pathogens that primarily infect intestinal epithelial cells. They cause actin restructuring and polymerization within the host cell to create an actin-rich protrusion below the site of adherence, termed the pedestal. Although there is clarity on the pathways initiating pedestal formation, the underlying purpose(s) of the pedestal remains ambiguous. The conservation of pedestal-forming activity across multiple pathogens and redundancy in formation pathways indicate a pathogenic advantage...
April 9, 2024: Infection and Immunity
Yikun Xing, Justin R Clark, James D Chang, Jacob J Zulk, Dylan M Chirman, Felipe-Andres Piedra, Ellen E Vaughan, Haroldo J Hernandez Santos, Kathryn A Patras, Anthony W Maresso
Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen's pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals...
April 9, 2024: Infection and Immunity
Tiffany N Harris-Jones, Jia Mun Chan, Kathleen T Hackett, Nathan J Weyand, Ryan E Schaub, Joseph P Dillard
Neisseria gonorrhoeae , a human restricted pathogen, releases inflammatory peptidoglycan (PG) fragments that contribute to the pathophysiology of pelvic inflammatory disease. The genus Neisseria is also home to multiple species of human- or animal-associated Neisseria that form part of the normal microbiota. Here we characterized PG release from the human-associated nonpathogenic species Neisseria lactamica and Neisseria mucosa and animal-associated Neisseria from macaques and wild mice. An N. mucosa strain and an N...
April 2, 2024: Infection and Immunity
Karine Melchior, Romana R Gerner, Suzana Hossain, Sean-Paul Nuccio, Cristiano Gallina Moreira, Manuela Raffatellu
The mouse pathogen Citrobacter rodentium is utilized as a model organism for studying infections caused by the human pathogens enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and to elucidate mechanisms of mucosal immunity. In response to C. rodentium infection, innate lymphoid cells and T cells secrete interleukin (IL)-22, a cytokine that promotes mucosal barrier function. IL-22 plays a pivotal role in enabling mice to survive and recover from C. rodentium infection, although the exact mechanisms involved remain incompletely understood...
April 1, 2024: Infection and Immunity
Adam J Lewis, Amanda C Richards, Alejandra A Mendez, Bijaya K Dhakal, Tiffani A Jones, Jamie L Sundsbak, Danelle S Eto, Alexis A Rousek, Matthew A Mulvey
Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here, we tested a panel of four well-studied phenolic compounds-caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate-for the effects on host cell adherence and invasion by uropathogenic Escherichia coli (UPEC)...
March 27, 2024: Infection and Immunity
Benjamin P Darwitz, Christopher J Genito, Lance R Thurlow
Diabetes mellitus, characterized by impaired insulin signaling, is associated with increased incidence and severity of infections. Various diabetes-related complications contribute to exacerbated bacterial infections, including hyperglycemia, innate immune cell dysfunction, and infection with antibiotic-resistant bacterial strains. One defining symptom of diabetes is hyperglycemia, resulting in elevated blood and tissue glucose concentrations. Glucose is the preferred carbon source of several bacterial pathogens, and hyperglycemia escalates bacterial growth and virulence...
March 25, 2024: Infection and Immunity
Megan T Williams, Yan Zhang, Mark E Pulse, Rance E Berg, Michael S Allen
Borrelia burgdorferi , the spirochetal agent of Lyme disease, utilizes a variety of strategies to evade and suppress the host immune response, which enables it to chronically persist in the host. The resulting immune response is characterized by unusually strong IgM production and a lack of long-term protective immunity. Previous studies in mice have shown that infection with B. burgdorferi also broadly suppresses host antibody responses against unrelated antigens. Here, we show that mice infected with B. burgdorferi and concomitantly immunized with recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein had an abrogated antibody response to the immunization...
March 22, 2024: Infection and Immunity
Sharie Keanne Ganchua, Pauline Maiello, Michael Chao, Forrest Hopkins, Douaa Mugahid, Philana Ling Lin, Sarah M Fortune, JoAnne L Flynn
Concomitant immunity is generally defined as an ongoing infection providing protection against reinfection . Its role in prevention of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is supported by epidemiological evidence in humans as well as experimental evidence in mice and non-human primates (NHPs). Whether the presence of live Mtb, rather than simply persistent antigen, is necessary for concomitant immunity in TB is still unclear. Here, we investigated whether live Mtb plays a measurable role in control of secondary Mtb infection...
March 22, 2024: Infection and Immunity
Anne-Sophie Bourrel, Amandine Picart, Jose-Carlos Fernandez, Constantin Hays, Virginie Mignon, Bruno Saubaméa, Claire Poyart, Agnès Fouet, Asmaa Tazi, Julie Guignot
Streptococcus agalactiae also named Group B Streptococcus (GBS) is the most significant pathogen causing invasive infections, such as bacteremia and meningitis, in neonates. Worldwide epidemiological studies have shown that a particular clonal complex (CC) of capsular serotype III, the CC17, is strongly associated with meningitis in neonates and is therefore, designated as the hypervirulent clone. Macrophages are a permissive niche for intracellular bacteria of all GBS clones. In this study, we deciphered the specific interaction of GBS CC17 strains with macrophages...
March 22, 2024: Infection and Immunity
Bo Huey Chiang, Giovanni Vega, Sarah C Dunwoody, Michael L Patnode
The intestinal lumen is a turbulent, semi-fluid landscape where microbial cells and nutrient-rich particles are distributed with high heterogeneity. Major questions regarding the basic physical structure of this dynamic microbial ecosystem remain unanswered. Most gut microbes are non-motile, and it is unclear how they achieve optimum localization relative to concentrated aggregations of dietary glycans that serve as their primary source of energy. In addition, a random spatial arrangement of cells in this environment is predicted to limit sustained interactions that drive co-evolution of microbial genomes...
March 20, 2024: Infection and Immunity
Xiaochen Hou, Cui Li, Jingyi Liu, Shanshan Yang, Xudong Peng, Qian Wang, Chengxiu Liu, Xing Liu, Junjie Luan, Guiqiu Zhao, Jing Lin
Aspergillus fumigatus ( A. fumigatus ) is one of the common pathogens of fungal keratitis. Fungal growth and invasion cause excessive inflammation and corneal damage, leading to severe vision loss. Neutrophils are the primary infiltrating cells critical for fungal clearance. Cathelicidin [LL-37 in humans and cathelicidin-related antimicrobial peptide (CRAMP) in mice], a natural antimicrobial peptide, can directly inhibit the growth of many pathogens and regulate immune responses. However, the role of cathelicidin and its effect on neutrophils in A...
March 19, 2024: Infection and Immunity
John-Demian Sauer, Mark J Mandel
No abstract text is available yet for this article.
March 14, 2024: Infection and Immunity
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