The Microbe, the Infection Enigma, and the Host DOI
Jean‐Laurent Casanova, Laurent Abel

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

The human genetic epidemiology of COVID-19 DOI Open Access
Mari Niemi, Mark J. Daly, Andrea Ganna

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(9), P. 533 - 546

Published: May 2, 2022

Language: Английский

Citations

119
From rare disorders of immunity to common determinants of infection: Following the mechanistic thread DOI Creative Commons
Jean‐Laurent Casanova, Laurent Abel

Cell, Journal Year: 2022, Volume and Issue: 185(17), P. 3086 - 3103

Published: Aug. 1, 2022

The immense interindividual clinical variability during any infection is a long-standing enigma. Inborn errors of IFN-γ and IFN-α/β immunity underlying rare infections with weakly virulent mycobacteria seasonal influenza virus have inspired studies two common infections: tuberculosis COVID-19. A TYK2 genotype impairing production accounts for about 1% cases, autoantibodies neutralizing account 15% critical COVID-19 cases. discovery inborn mechanisms drove the identification monogenic or autoimmune determinants related infections. This “rare-to-common” genetic mechanistic approach to infectious diseases may be heuristic value.

Language: Английский

Citations

106
Human autoantibodies underlying infectious diseases DOI Creative Commons
Anne Puel, Paul Bastard, Jacinta Bustamante

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(4)

Published: March 23, 2022

The vast interindividual clinical variability observed in any microbial infection—ranging from silent infection to lethal disease—is increasingly being explained by human genetic and immunological determinants. Autoantibodies neutralizing specific cytokines underlie the same infectious diseases as inborn errors of corresponding cytokine or response pathway. against type I IFNs COVID-19 pneumonia adverse reactions live attenuated yellow fever virus vaccine. II IFN severe disease caused environmental tuberculous mycobacteria, other intra-macrophagic microbes. IL-17A/F IL-6 are less common mucocutaneous candidiasis staphylococcal diseases, respectively. Inborn autoantibodies GM-CSF pulmonary alveolar proteinosis; associated infections well characterized. In individual patients, preexist with pathogen concerned disease. Human antibody-driven autoimmunity can interfere that essential for protective immunity agents but otherwise redundant, thereby underlying diseases.

Language: Английский

Citations

97
Advances in the application of molecular diagnostic techniques for the detection of infectious disease pathogens (Review) DOI Creative Commons
Qingqing Liu, Xiaojuan Jin, Jun Cheng

et al.

Molecular Medicine Reports, Journal Year: 2023, Volume and Issue: 27(5)

Published: April 3, 2023

Infectious diseases are a major global cause of morbidity and mortality, seriously affecting public health socioeconomic stability. Since infectious can be caused by wide variety pathogens with similar clinical manifestations symptoms that difficult to accurately distinguish, selecting the appropriate diagnostic techniques for rapid identification is crucial disease diagnosis management. However, traditional have low detection rates, long times limited automation, which means they do not meet requirements diagnosis. Recent years seen continuous developments in molecular technology, has higher sensitivity specificity, shorter time increased performs an important role early pathogens. The present study summarizes recent progress technologies such as PCR, isothermal amplification, gene chips high‑throughput sequencing pathogens, compares technical principles, advantages disadvantages, applicability costs these techniques.

Language: Английский

Citations

84
Naringenin: A flavanone with anti-inflammatory and anti-infective properties DOI Open Access

Cai Ji,

Hongli Wen,

He Zhou

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114990 - 114990

Published: June 12, 2023

Although a growing body of research has recently shown how crucial inflammation and infection are to all major diseases, several the medications currently available on market have various unfavourable side effects, necessitating development alternative therapeutic choices. Researchers increasingly interested in or active components derived from natural sources. Naringenin is commonly consumed flavonoid found many plants, since it was discovered nutritional benefits, been utilized treat infections caused by particular bacteria viruses. However, absence adequate clinical data naringenin's poor solubility stability severely restrict its usage as medicinal agent. In this article, we discuss effects mechanisms action autoimmune-induced inflammation, bacterial infections, viral based recent research. We also present few suggestions for enhancing solubility, stability, bioavailability. This paper emphasizes potential use naringenin an anti-inflammatory anti-infective agent next prophylactic substance treatment inflammatory infectious even though some still unclear, offers theoretical support application.

Language: Английский

Citations

83
Autoantibodies against type I IFNs in patients with critical influenza pneumonia DOI Creative Commons
Qian Zhang, Andrés Pizzorno, Lisa Miorin

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(11)

Published: Sept. 16, 2022

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies IFN-α2 alone (five patients) or with IFN-ω (eight from a cohort of 279 (4.7%) aged 6–73 yr influenza pneumonia. Nine four had antibodies high low concentrations, respectively, IFN-α2, six two IFN-ω. The patients’ increased A virus replication in both A549 cells reconstituted human airway epithelia. prevalence these was significantly higher than that the general population for <70 age (5.7 vs. 1.1%, P = 2.2 × 10−5), but not >70 (3.1 4.4%, 0.68). risk highest concentrations (OR 11.7, 1.3 especially those old 139.9, 3.1 10−10). also identified 10 additional patient cohorts. IFNs account ∼5% cases life-threatening old.

Language: Английский

Citations

81
Type I interferons and SARS-CoV-2: from cells to organisms DOI Creative Commons
Paul Bastard, Qian Zhang, Shen‐Ying Zhang

et al.

Current Opinion in Immunology, Journal Year: 2022, Volume and Issue: 74, P. 172 - 182

Published: Jan. 25, 2022

Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type IFNs SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of IFNs, proteins can inhibit various steps IFN production response. Exogenous viral growth vitro. In animal species vivo, deficiencies underlie higher loads more severe disease than control animals. The early administration exogenous improves infection control. humans, inborn errors of, auto-antibodies against life-threatening COVID-19 pneumonia. Overall, are essential for host defense individual whole organisms.

Language: Английский

Citations

71
Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria DOI Creative Commons
Jérémie Rosain, Anna‐Lena Neehus, Jérémy Manry

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(3), P. 621 - 645.e33

Published: Feb. 1, 2023

Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn IFN-α/β-dependent intrinsic viral diseases. Both types IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria related intramacrophagic pathogens. These have no history severe disease, despite exposure to many viruses, including SARS-CoV-2, which is in individuals impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated vitro, IRF1-dependent responses IFN-γ are, both quantitatively qualitatively, much stronger than those IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control pathogens normally when IFN-γ. By contrast, nine almost normal fibroblasts. Human essential for mycobacteria, but largely redundant antiviral

Language: Английский

Citations

66
Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria DOI
Quentin Philippot, Masato Ogishi, Jonathan Bohlen

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(80)

Published: Feb. 3, 2023

Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 deficiency display Mendelian susceptibility to mycobacterial disease (MSMD) due impaired IFN-γ production and, less commonly, chronic mucocutaneous candidiasis (CMC) IL-17A/F production. We report six patients from four kindreds AR IL-23R deficiency. These are homozygous for one of different loss-of-function IL23R variants. All have a history MSMD, but only two suffered CMC. show that IL-23 induces IL-17A in MAIT cells, possibly contributing the incomplete penetrance CMC unresponsive IL-23. By contrast, is required both baseline and Mycobacterium -inducible immunity Vδ2 + γδ T probably higher MSMD these patients. Human appears contribute IL-17A/F–dependent Candida single lymphocyte subset IFN-γ–dependent at least subsets.

Language: Английский

Citations

48
Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs DOI Creative Commons
Jean‐Laurent Casanova, Mark S. Anderson

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(3)

Published: Jan. 31, 2023

Since 2003, rare inborn errors of human type I IFN immunity have been discovered, each underlying a few severe viral illnesses. Autoantibodies neutralizing IFNs due to autoimmune regulator (AIRE)-driven T cell tolerance were discovered in 2006, but not initially linked any disease. These two lines clinical investigation converged 2020, with the discovery that inherited and/or deficiencies accounted for approximately 15%-20% cases critical COVID-19 pneumonia unvaccinated individuals. Thus, insufficient at onset SARS-CoV-2 infection may be general determinant life-threatening COVID-19. findings illustrate unpredictable, considerable, contribution study genetic diseases basic biology and public health.

Language: Английский

Citations

46