Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection DOI Open Access
Anna Zychlinsky Scharff, Matthieu Rousseau, Lívia Lacerda Mariano

et al.

JCI Insight, Journal Year: 2019, Volume and Issue: 4(13)

Published: May 30, 2019

Sex-based differences influence incidence and outcome of infectious disease. Women have a significantly greater urinary tract infection (UTI) than men, yet, conversely, male UTI is more persistent with associated morbidity. Mechanisms underlying these sex-based are unknown, in part due to lack experimental models. We optimized model transurethrally infect mice directly compared both sexes. Although sexes were initially equally colonized by uropathogenic E. coli, only testosterone-treated female remained chronically infected for up 4 weeks. Female had robust innate responses, including higher IL-17 expression, increased γδ T cells group 3 lymphoid the bladder following infection. Accordingly, neutralizing abolished resolution mice, identifying cytokine pathway necessary bacterial clearance. Our findings support concept that responses contribute impaired immunity males provide rationale non-antibiotic-based immune targeting improve response UTI.

Language: Английский

Considering how biological sex impacts immune responses and COVID-19 outcomes DOI Creative Commons
Eileen P. Scully, Jenna Haverfield, Rebecca L. Ursin

et al.

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(7), P. 442 - 447

Published: June 11, 2020

Language: Английский

Citations

890
Sexual-dimorphism in human immune system aging DOI Creative Commons
Eladio J. Márquez, Cheng‐Han Chung,

Radu Marcheş

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Feb. 6, 2020

Differences in immune function and responses contribute to health- life-span disparities between sexes. However, the role of sex system aging is not well understood. Here, we characterize peripheral blood mononuclear cells from 172 healthy adults 22-93 years age using ATAC-seq, RNA-seq, flow cytometry. These data reveal a shared epigenomic signature including declining naïve T cell increasing monocyte cytotoxic functions. changes are greater magnitude men accompanied by male-specific decline B-cell specific loci. Age-related first spike around late-thirties with similar timing sexes, whereas second earlier stronger men. Unexpectedly, genomic differences sexes increase after 65, having higher innate pro-inflammatory activity lower adaptive activity. Impact on phenotypes can be visualized at https://immune-aging.jax.org provide insights into future studies.

Language: Английский

Citations

412
Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors DOI
Étienne Patin, Milena Hasan, Jacob Bergstedt

et al.

Nature Immunology, Journal Year: 2018, Volume and Issue: 19(3), P. 302 - 314

Published: Feb. 20, 2018

Language: Английский

Citations

260
The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives DOI Creative Commons
Christophe d’Enfert,

Ann-Kristin Kaune,

Leovigildo-Rey Alaban

et al.

FEMS Microbiology Reviews, Journal Year: 2020, Volume and Issue: 45(3)

Published: Nov. 18, 2020

Candida albicans is a major fungal pathogen of humans. It exists as commensal in the oral cavity, gut or genital tract most individuals, constrained by local microbiota, epithelial barriers and immune defences. Their perturbation can lead to outgrowth development mucosal infections such oropharyngeal vulvovaginal candidiasis, patients with compromised immunity are susceptible life-threatening systemic infections. The importance interplay between fungus, host microbiota driving transition from C. commensalism pathogenicity widely appreciated. However, complexity these interactions, significant impact fungal, variability upon disease severity outcome, less well understood. Therefore, we summarise features fungus that promote infection, how genetic variation clinical isolates influences pathogenicity. We discuss antifungal immunity, this differs mucosae, individual person's susceptibility infection. Also, describe factors influence composition gut, vaginal microbiotas, affect colonisation immunity. argue detailed understanding variables, which underlie fungal-host-microbiota will present opportunities for directed therapies benefit vulnerable patients.

Language: Английский

Citations

236
<p>Immunoinformatics and Vaccine Development: An Overview</p> DOI Creative Commons
Angus Nnamdi Oli,

Wilson Okechukwu Obialor,

M Ifeanyichukwu

et al.

ImmunoTargets and Therapy, Journal Year: 2020, Volume and Issue: Volume 9, P. 13 - 30

Published: Feb. 1, 2020

Abstract: The use of vaccines have resulted in a remarkable improvement global health. It has saved several lives, reduced treatment costs and raised the quality animal human lives. Current traditional came empirically with either vague or completely no knowledge how they modulate our immune system. Even at face potential vaccine design advance, immune-related concerns (as seen specific vulnerable populations, cases emerging/re-emerging infectious disease, pathogens complex lifecycle antigenic variability, need for personalized vaccinations, vaccines' immunological safety -specifically likelihood to trigger non-antigen-specific responses that may cause autoimmunity allergy) are being raised. And these driven immunologists toward research better approach will consider challenges. Currently, immunoinformatics paved way understanding some disease pathogenesis, diagnosis, system response computational vaccinology. importance this study diseases is diverse terms approaches used, but united by common qualities related host–pathogen relationship. Bioinformatics methods also used assign functions uncharacterized genes which can be targeted as candidate inclusion women pregnant into trials programs. essence review give insight focus on novel computational, experimental computation-driven studying interactions thus making case its development. Keywords: immunoinformatics, vaccinology, design, emerging infections, system; vaccinology

Language: Английский

Citations

211
ImmGen report: sexual dimorphism in the immune system transcriptome DOI Creative Commons
Shani T. Gal-Oz, Bárbara Maier, Hideyuki Yoshida

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 20, 2019

Abstract Sexual dimorphism in the mammalian immune system is manifested as more frequent and severe infectious diseases males and, on other hand, higher rates of autoimmune disease females, yet insights underlying those differences are still lacking. Here we characterize sex by RNA ATAC sequence profiling untreated interferon-induced cell types male female mice. We detect very few differentially expressed genes between cells except macrophages from three different tissues. Accordingly, genomic regions display accessibility sexes. Transcriptional sexual mediated innate pathways, increases after interferon stimulation. Thus, stronger response females may be due to activated pathways prior pathogen invasion.

Language: Английский

Citations

208
Impaired NLRP3 inflammasome activation/pyroptosis leads to robust inflammatory cell death via caspase-8/RIPK3 during coronavirus infection DOI Creative Commons
Min Zheng, Evan P. Williams, R. K. Subbarao Malireddi

et al.

Journal of Biological Chemistry, Journal Year: 2020, Volume and Issue: 295(41), P. 14040 - 14052

Published: Aug. 6, 2020

Coronaviruses have caused several zoonotic infections in the past two decades, leading to significant morbidity and mortality globally. Balanced regulation of cell death inflammatory immune responses is essential promote protection against coronavirus infection; however, underlying mechanisms that control these processes remain be resolved. Here we demonstrate infection with murine mouse hepatitis virus (MHV) activated NLRP3 inflammasome form PANoptosis. Deleting components or downstream executioner gasdermin D (GSDMD) led an initial reduction followed by a robust increase incidence caspase-8- receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated deathafter infection. Additionally, loss GSDMD promoted activation. Moreover, amounts some cytokines released during were significantly altered absence GSDMD. Altogether, our findings show death, PANoptosis, induced impaired function pyroptosis can lead negative consequences for host. These may important implications studies coronavirus-induced disease.

Language: Английский

Citations

172
Human immune diversity: from evolution to modernity DOI Open Access
Adrian Liston, Stéphanie Humblet‐Baron, Darragh Duffy

et al.

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(12), P. 1479 - 1489

Published: Nov. 18, 2021

Language: Английский

Citations

132
From GWAS to Gene: Transcriptome-Wide Association Studies and Other Methods to Functionally Understand GWAS Discoveries DOI Creative Commons
Binglan Li, Marylyn D. Ritchie

Frontiers in Genetics, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 30, 2021

Since their inception, genome-wide association studies (GWAS) have identified more than a hundred thousand single nucleotide polymorphism (SNP) loci that are associated with various complex human diseases or traits. The majority of GWAS discoveries located in non-coding regions the genome and unknown functions. valley between downstream affected genes hinders investigation disease mechanism utilization genetics for improvement clinical care. Meanwhile, advances high-throughput sequencing technologies reveal important genomic regulatory roles play transcriptional activities genes. In this review, we focus on data integrative bioinformatics methods combine functional genomics knowledge to identify genetically regulated We categorize describe two types methods. First, fine-mapping Fine-mapping is an exploratory approach calibrates likely causal variants underneath signals. connect signals potentially through statistical and/or annotations. Second, discuss gene-prioritization These hypothesis generating approaches evaluate whether genetic regulate via certain mechanisms influence traits, including colocalization, mendelian randomization, transcriptome-wide study (TWAS). TWAS gene-based investigates associations gene expression has gained popularity over years due its ability reduce multiple testing burden comparison other variant-based analytic approaches. Multiple been developed varied methodological designs biological hypotheses past 5 years. dive into discussions how differ many aspects challenges different face. Overall, powerful tool identifying trait-associated With advent single-cell sequencing, chromosome conformation capture, editing technologies, multiplexing reporter assays, expecting comprehensive understanding regulation underlying traits future.

Language: Английский

Citations

114
Sex and Gender Differences in Bacterial Infections DOI
Sara P. Dias, Matthijs C. Brouwer, Diederik van de Beek

et al.

Infection and Immunity, Journal Year: 2022, Volume and Issue: 90(10)

Published: Sept. 19, 2022

There is a growing awareness of the importance sex and gender in medicine research. Women typically have stronger immune responses to self foreign antigens than men, resulting sex-based differences autoimmunity infectious diseases.

Language: Английский

Citations

95