The Microbe, the Infection Enigma, and the Host

Annual Review of Microbiology, Journal Year: 2024, Volume and Issue: 78(1), P. 103 - 124

Published: July 10, 2024

Human infectious diseases are unique in that the discovery of their environmental trigger, microbe, was sufficient to drive development extraordinarily effective principles and tools for prevention or cure. This medical prowess has outpaced, perhaps even hindered, scientific progress equal magnitude biological understanding diseases. Indeed, hope kindled by germ theory disease rapidly subdued infection enigma, need a host solution, when it realized most individuals infected with agents continue do well. The root causes death unhappy few remained unclear. While canonical approaches vitro (cellular microbiology), vivo (animal models), natura (clinical studies) analyzed consequences considered be cause disease, cells, tissues, organisms seen as uniform host, alternative searched preexisting particularly human genetic immunological determinants populations diverse trigger microbe.

Language: Английский

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Tissue-resident skeletal muscle macrophages promote recovery from viral pneumonia-induced sarcopenia in normal aging.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract Sarcopenia, which diminishes lifespan and healthspan in the elderly, is commonly exacerbated by viral pneumonia, including influenza COVID-19. In a study of A pneumonia mice, young mice fully recovered from sarcopenia, while older did not. We identified population tissue-resident skeletal muscle macrophages that form spatial niche with satellite cells myofibers but are lost age. Mice gain-of-function mutation Mertk receptor maintained this macrophage-myofiber interaction during aging influenza-induced sarcopenia. contrast, deletion or loss Cx3cr1 disrupted niche, preventing regeneration. Heterochronic parabiosis not restore old mice. These findings suggest age-related disrupts cellular signaling necessary for regeneration after offering potential target to mitigate sarcopenia aging.

Language: Английский

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Genetic diversity of the immunoglobulin heavy chain locus in cohorts of patients affected with SARS-CoV-2

Human Genomics, Journal Year: 2025, Volume and Issue: 19(1)

Published: Jan. 30, 2025

Language: Английский

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Human genetics of Whipple's disease

Current Opinion in Rheumatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Whipple's disease (WD), triggered by Tropheryma whipplei ( T. ), is a rare, chronic, inflammatory, systemic infectious that typically manifests in adults. The most frequent initial manifestations include arthritis, followed diarrhea, abdominal pain, and weight loss. Half the world's population exposed to , but only one million develop WD. This suggests acquired or inborn errors of immunity (IEI) may underlie Anti-TNF treatment well established risk factor for flare-ups We have also reported two rare IEI patients with Six WD from unrelated kindreds were found autosomal dominant IRF4 deficiency acting via mechanism haploinsufficiency. These otherwise healthy. In addition, single patient history other infections was recessive CD4 deficiency. Rare can Human genetic studies are warranted development precision medicine affected improve our understanding pathogenesis this disease.

Language: Английский

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Sepsis in patients who are immunocompromised: diagnostic challenges and future therapies

The Lancet Respiratory Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Age‐Related Oxidative Stress and Mitochondrial Dysfunction in Lymph Node Stromal Cells Limit the Peripheral T Cell Homeostatic Maintenance and Function

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: May 21, 2025

ABSTRACT Lymph nodes (LN) are the key organs in charge of long‐term maintenance naïve lymphocytes and their initial, primary activation upon infection. Accumulating evidence indicates that LN stromal cells undergo degenerative changes with aging critically impair function, including generation protective immune responses. The nature these defects remains incompletely understood. We here demonstrate age‐related manifest themselves mitochondrial dysfunction oxidative stress. Ex vivo, all three major cell subsets, fibroblastic reticular (FRC), lymphatic endothelial (LEC), blood (BEC) exhibit elevated reactive oxygen species (ROS) stress, reduced potential, mass aging. Old FRC also exhibited cytoplasmic ROS production. This was accompanied by ability old to support Tn survival vitro, a defect alleviated pretreating stroma general antioxidant N ‐acetyl cysteine (NAC) as well ROS‐reducing (mitoquinone) mitophagy‐inducing (urolithin A) compounds. Mitochondrial and, particular, potential were seen vaccination or infection vivo. Consistent results, vivo treatment mice NAC restored adult levels numbers antigen‐specific CD8 + effector T production granzyme B response antigenic challenge.

Language: Английский

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Genetic defects of brain immunity in childhood herpes simplex encephalitis

Nature, Journal Year: 2024, Volume and Issue: 635(8039), P. 563 - 573

Published: Nov. 20, 2024

Language: Английский

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