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

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19 DOI Creative Commons
Qian Zhang, Paul Bastard, Zhiyong Liu

et al.

Science, Journal Year: 2020, Volume and Issue: 370(6515)

Published: Sept. 24, 2020

The genetics underlying severe COVID-19 immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody dampens IFN response prevent damage from pathogen-induced inflammation. Two studies now examine likelihood affects risk of coronavirus disease 2019 (COVID-19) through components this (see Perspective by Beck Aksentijevich). Q. Zhang et al. used a candidate gene approach identified patients with who have mutations in genes involved regulation type I III immunity. They found enrichment these conclude may determine clinical course infection. Bastard individuals high titers neutralizing autoantibodies against IFN-α2 IFN-ω about 10% pneumonia. These were not either infected people asymptomatic or had milder phenotype healthy individuals. Together, identify means which at highest life-threatening identified. Science , issue p. eabd4570 eabd4585 ; see also 404

Language: Английский

Citations

2178
Human genetic and immunological determinants of critical COVID-19 pneumonia DOI Open Access
Qian Zhang, Paul Bastard, Adem Karbuz

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 587 - 598

Published: Jan. 28, 2022

Language: Английский

Citations

323
The type I interferonopathies: 10 years on DOI Open Access
Yanick J. Crow, Daniel B. Stetson

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(8), P. 471 - 483

Published: Oct. 20, 2021

Language: Английский

Citations

314
A Global Effort to Define the Human Genetics of Protective Immunity to SARS-CoV-2 Infection DOI Creative Commons
Jean‐Laurent Casanova, Helen C. Su, Laurent Abel

et al.

Cell, Journal Year: 2020, Volume and Issue: 181(6), P. 1194 - 1199

Published: May 13, 2020

Language: Английский

Citations

217
Immune-mediated inflammatory disease therapeutics: past, present and future DOI Open Access
Iain B. McInnes, Ellen M. Gravallese

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(10), P. 680 - 686

Published: Sept. 13, 2021

Language: Английский

Citations

209
Host genetics and infectious disease: new tools, insights and translational opportunities DOI Open Access
Andrew Kwok, Alexander J. Mentzer, Julian C. Knight

et al.

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(3), P. 137 - 153

Published: Dec. 4, 2020

Language: Английский

Citations

180
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies DOI Creative Commons
Jérémy Manry, Paul Bastard, Adrian Gervais

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(21)

Published: May 16, 2022

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It important to estimate their quantitative impact on mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence these risk death increase with higher in men. Using an unvaccinated sample 1,261 deceased patients 34,159 individuals from general population, we found against IFNs strongly increased infection fatality rate at all ages, men women. Autoantibodies common predictors COVID-19. Testing for should be considered population.

Language: Английский

Citations

160
Mucosal immune responses to infection and vaccination in the respiratory tract DOI Creative Commons
Robert C. Mettelman, E. Kaitlynn Allen, Paul G. Thomas

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(5), P. 749 - 780

Published: May 1, 2022

Language: Английский

Citations

156
SARS-CoV-2–related MIS-C: A key to the viral and genetic causes of Kawasaki disease? DOI Creative Commons
Vanessa Sancho‐Shimizu, Petter Brodin, Aurelié Cobat

et al.

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(6)

Published: April 27, 2021

Multisystem inflammatory syndrome in children (MIS-C) emerged April 2020 communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known poorly understood and clinically pediatric for which weak associations have been found myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 the trigger MIS-C, typically occurs about 1 mo after infection. These findings support hypothesis triggers various forms classic KD. We further suggest rare inborn errors immunity (IEIs) altering immune response to may underlie pathogenesis MIS-C some children. The discovery monogenic IEIs underlying would shed light on its pathogenesis, paving way genetic approach KD, revisited as heterogeneous collection viruses.

Language: Английский

Citations

135
Mechanisms of viral inflammation and disease in humans DOI
Jean‐Laurent Casanova, Laurent Abel

Science, Journal Year: 2021, Volume and Issue: 374(6571), P. 1080 - 1086

Published: Nov. 25, 2021

Disease and accompanying inflammation are uncommon outcomes of viral infection in humans. Clinical occurs if steady-state cell-intrinsic leukocytic immunity to viruses fails. Inflammation attests the attempts newly recruited activated leukocytes resolve blood or tissues. In confusing battle between a myriad cells, studies human genetics can separate root cause disease from its consequences. Single-gene inborn errors underlying diverse infections skin, brain, lungs help clarify determinants disease. The genetic elucidation immunological deficits single patient with specific vulnerability profile reveal mechanisms that may be triggered by other causes, inherited otherwise, patients. This dissection is giving rise new biology medicine.

Language: Английский

Citations

122