We have shown previously that peripheral lymph node-resident retinoic acid receptor-related orphan receptor γt+ NK1.1− invariant NKT (iNKT) cells produce IL-17A independently of IL-6. In this study, we show that the concomitant presence of IL-1 and IL-23 is crucial to induce a rapid and sustained IL-17A/F and IL-22 response by these cells that requires TCR–CD1d interaction and partly relies on IL-23–mediated upregulation of IL-23R and IL-1R1 expression. We further show that IL-1 and IL-23 produced by pathogen-associated molecular pattern-stimulated dendritic cells induce this response from NK1.1− iNKT cells in vitro, involving mainly TLR2/4-signaling pathways. Finally, we found that IL-17A production by these cells occurs very early and transiently in vivo in response to heat-killed bacteria. Overall, our study indicates that peripheral lymph node NK1.1− iNKT cells could be a source of innate Th17-related cytokines during bacterial infections and supports the hypothesis that they are able to provide an efficient first line of defense against bacterial invasion.

Background Growing consideration is emerging regarding the burden of persisting sequelae after SARS-CoV-2 infection. Out-patients exhibiting long Covid may benefit from ambulatory rehabilitation which is, to date, poorly documented. Methods A longitudinal follow-up over a one-year period was conducted in two ambulatory rehabilitation structures in order to describe the characteristics of real-life patients referred with Covid-19 sequelae and their evolution over the course of rehabilitation. Results 39 consecutive patients were included from April 1 st 2020 to April 1 st 2021. Patients were middle-aged (48±15yr), without comorbidities, and mostly mild to moderate SARS-CoV-2 infection (25(64%) not requiring hospitalisation). Rehabilitation referral was considered with a median delay of 73[34-178] days after disease onset. Most prevalent symptoms were dyspnoea (n=35(90%)) and fatigue (n=30(77%)). Hyperventilation syndrome was highly frequent (n=12(34%)). 29(74%) patients presented with prolonged functional sequelae, which was associated with younger age (43±14 vs . 50±10yr; p=0.002), greater prevalence of hyperventilation syndrome (n=12(41%) vs . 0(0%); p=0.255) and poorer quality of life (VQ-11; 31±10 vs . 23±9; p=0.030). Over the course of rehabilitation, exertional dyspnoea, 6-minutes walking distance, 3-minutes sit-to-stand test, hyperventilation syndrome prevalence and quality of life significantly improved. Conclusion Hyperventilation is frequent in long Covid and may explain persistent dyspnoea as well as altered quality of life. Our data support screening of hyperventilation syndrome and functional impairment in mild Covid-19 out-patients as both of these components may improve with ambulatory rehabilitation.