COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors involved in COVID-19–driven ARDS are poorly understood. Here, in blood and airways of severe COVID-19 patients, we serially analyzed unconventional T cells, a heterogeneous class of T lymphocytes (MAIT, γδT, and iNKT cells) with potent antimicrobial and regulatory functions. Circulating unconventional T cells of COVID-19 patients presented with a profound and persistent phenotypic alteration. In the airways, highly activated unconventional T cells were detected, suggesting a potential contribution in the regulation of local inflammation. Finally, expression of the CD69 activation marker on blood iNKT and MAIT cells of COVID-19 patients on admission was predictive of clinical course and disease severity. Thus, COVID-19 patients present with an altered unconventional T cell biology, and further investigations will be required to precisely assess their functions during SARS–CoV-2–driven ARDS.

Lung-resident memory B cells (BRM cells) are elicited after influenza infections of mice, but connections to other pathogens and hosts — as well as their functional significance — have yet to be determined. We postulate that BRM cells are core components of lung immunity. To test this, we examined whether lung BRM cells are elicited by the respiratory pathogen pneumococcus, are present in humans, and are important in pneumonia defense. Lungs of mice that had recovered from pneumococcal infections did not contain organized tertiary lymphoid organs, but did have plasma cells and noncirculating memory B cells. The latter expressed distinctive surface markers (including CD69, PD-L2, CD80, and CD73) and were poised to secrete antibodies upon stimulation. Human lungs also contained B cells with a resident memory phenotype. In mice recovered from pneumococcal pneumonia, depletion of PD-L2⁺ B cells, including lung BRM cells, diminished bacterial clearance and the level of pneumococcus-reactive antibodies in the lung. These data define lung BRM cells as a common feature of pathogen-experienced lungs and provide direct evidence of a role for these cells in pulmonary antibacterial immunity.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways caused mainly by cigarette smoke exposure. COPD progression is marked by exacerbations of the disease, often associated with infections. Recent data show the involvement in COPD pathophysiology of interleukin (IL)-17 and IL-22, two cytokines that are important in the control of lung inflammation and infection. During the initiation and progression of the disease, increased IL-17 secretion causes neutrophil recruitment, leading to chronic inflammation, airways obstruction and emphysema. In the established phase of COPD, a defective IL-22 response facilitates pathogen-associated infections and disease exacerbations. Altered production of these cytokines involves a complex network of immune cells and dysfunction of antigen-presenting cells. In this review, we describe current knowledge on the involvement of IL-17 and IL-22 in COPD pathophysiology at steady state and during exacerbations, and discuss implications for COPD management and future therapeutic approaches.

Introduction: Herpes simplex encephalitis (HSE) is a rare disease with a poor prognosis. No recent evaluation of hospital incidence, acute mortality and morbidity is available. In particular, decompressive craniectomy has rarely been proposed in cases of life-threatening HSE with temporal herniation, in the absence of evidence. This study aimed to assess the hospital incidence and mortality of HSE, and to evaluate the characteristics, management, the potential value of decompressive craniectomy and the outcome of patients with HSE admitted to intensive care units (ICUs). Methods: Epidemiological study: we used the hospital medical and administrative discharge database to identify hospital stays, deaths and ICU admissions relating to HSE in 39 hospitals, from 2010 to 2013. Retrospective monocentric cohort: all patients with HSE admitted to the ICU of the university hospital during the study were included. The use of decompressive craniectomy and long-term outcome were analyzed. The initial brain images were analyzed blind to outcome. Results: The hospital incidence of HSE was 1.2/100,000 inhabitants per year, 32 % of the patients were admitted to ICUs and 17 % were mechanically ventilated. Hospital mortality was 5.5 % overall, but was as high as 11.9 % in ICUs. In the monocentric cohort, 87 % of the patients were still alive after one year but half of them had moderate to severe disability. Three patients had a high intracranial pressure (ICP) with brain herniation and eventually underwent decompressive hemicraniectomy. The one-year outcome of these patients did not seem to be different from that of the other patients. It was not possible to predict brain herniation reliably from the initial brain images. Conclusions: HSE appears to be more frequent than historically reported. The high incidence we observed probably reflects improvements in diagnostic performance (routine use of PCR). Mortality during the acute phase and long-term disability appear to be stable. High ICP and brain herniation are rare, but must be monitored carefully, as initial brain imaging is not useful for identifying high-risk patients. Decompressive craniectomy may be a useful salvage procedure in cases of intractable high ICP.