Physiological costs of facultative endosymbionts in aphids assessed from energy metabolism

International audienceMany insect species harbour heritable bacterial endosymbionts. Some facultative endosymbionts provide benefits to their hosts under certain environmental conditions. Facultative endosymbionts are expected to impose additional energetic expenditures to their host, reducing host fitness. While there is accumulating evidence in plant sucking insects that facultative endosymbionts reduce the fitness of their host under permissive conditions, no direct energy costs associated with facultative endosymbionts have been identified. Using the standard metabolic rate (SMR) as a measure of the energy cost of self-maintenance, we investigated whether two common facultative endosymbionts Hamiltonella defensa or Regiella insecticola increase the maintenance cost of the pea aphid Acyrthosiphon pisum which could translate into host fitness reduction ('compensation hypothesis'). In addition, we tested if there was a link between SMR and the aphid fitness and whether it depended on endosymbiont density and aphid energetic reserves. Finally, we measured SMR at different temperatures to assess the impact of suboptimal thermal conditions on physiological cost of endosymbionts. In the presence of facultative endosymbionts, aphids expressed generally a lower fitness and a higher SMR compared to uninfected ones, in accordance with the 'compensation hypothesis'. However, the SMR difference between infected and uninfected aphids tended to decrease with increasing temperature. Complex host genotype-by-symbiont genotype-by-temperature interactions on SMR were also revealed. Energetic budget of adult aphids appeared weakly influenced by the aphid genotype and endosymbiont species, suggesting that facultative endosymbionts primarily impact the consumption of energy resources rather than their acquisition. Density of facultative endosymbionts varied largely among aphid lines but was not associated with the fitness nor metabolic rate of aphids. This work supports the energy basis of facultative endosymbiont associated fitness costs and raises new questions about the effect of facultative endosymbionts on the energy metabolism of their host. Read the free Plain Language Summary for this article on the Journal blog

Outbreak of hemolytic uremic syndrome with unusually severe clinical presentation caused by Shiga toxin-producing Escherichia coli O26:H11 in France

International audienceBackground: In spring 2019, an outbreak of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC HUS) occurred in France. Epidemiological investigations made by Santé publique France in connection with microbiological investigations at the national reference center for STEC promptly identified a common exposure to consumption of raw cow's milk cheese, and confirmed a cluster affiliation of the E. coli O26:H11 outbreak strain. Here, we report the clinical characteristics of the patients, the treatment used, as well as the outcome at 1 month.Method: Patients with STEC HUS linked to the E. coli O26:H11 outbreak strain were identified from the national surveillance network of pediatric STEC HUS cases coordinated by Santé publique France.Clinical data were analyzed from the patients’ hospital records obtained from the treating physicians.Results: Overall, 20 pediatric cases of STEC HUS linked to the outbreak strain were identified. Their median age of the patients was 16 months (range: 5–60). Most of them presented with diarrhea but none had received prior antibiotherapy. A total of 13 patients required dialysis; 10 patients and four patients had central nervous system (CNS) and cardiac involvement, respectively. No deaths occurred. At the 1-month follow-up, only two patients had a decreased glomerular filtration rate, below 80 mL /min/1.73m2 and four had hypertension. One patient had neurological sequelae.Conclusion: The E. coli O26:H11 strain identified as the cause of an STEC HUS outbreak in France in spring 2019 is notable for the initial severe clinical presentation of the patients, with a particularly high frequency of CNS and cardiac involvement similar to the German E. coli O104:H4 outbreak described in 2011. However, despite the initial severity, the 1-month outcome was favorable in most cases. The patients’ young age in this outbreak highlights the need to improve information and caregiver awareness regarding consumption of at-risk foods by young children as key preventive measures against STEC infections

Acute tubulointerstitial nephritis with or without uveitis: a novel form of post-acute COVID-19 syndrome in children

International audienceMultiorgan sequelae of coronavirus disease 2019 (COVID-19) beyond the acute phase of infection are increasingly described as clinical experience expands. In children, acute COVID-19 appears to be generally asymptomatic or mild. Yet, the multisystem inflammatory syndrome in children (MIS-C) may be a severe postinfectious complication following exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 During the first pandemic year, we observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with uveitis (TINUs) among children. Causes of aTIN include drugs, infections, and systemic diseases, but often remain undetermined. The rare TINUs syndrome associating aTIN and uveitis is considered to result from a still ill-characterized immune-mediated process. The observed increased incidence of idiopathic aTIN/TINUs prompted us to examine whether SARS-CoV-2 might be the initial trigger

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

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

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

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

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old