Nature Reviews Immunology最新文献

Infectious diseases pose a particular risk to newborns and there is a global need to protect this vulnerable group. Because of the challenges of developing vaccines that are effective in newborns, only the hepatitis B and tuberculosis vaccines are given in the first 28 days of life, and even those vaccines are mainly only offered to high-risk groups. Maternal antibodies cross the placenta and can afford some protection to the newborn, so an alternative strategy is vaccination in pregnancy. This approach has been successfully used to protect newborns against tetanus and pertussis, and vaccines that are primarily offered to protect the mother during pregnancy, such as influenza and COVID-19 vaccines, also provide some protection to newborns. A respiratory syncytial virus vaccine has recently been approved for use in pregnancy to protect newborns, and a new vaccine that will be offered during pregnancy to prevent Group B Streptococcus infection in infants is on the horizon. Here, we discuss the current vaccines that are offered during pregnancy and to newborns, the vaccines in development for future use in these groups and the challenges that remain concerning the delivery and uptake of such vaccines.

The cells in barrier tissues can distinguish pathogenic from commensal bacteria and target inflammatory responses only in the context of infection. As such, these cells must be able to identify pathogen infection specifically and not just the presence of an infectious organism, because many innocuous bacteria express the ligands that activate innate immunity in other contexts. Unravelling the mechanisms that underly this specificity, however, is challenging. Free-living nematodes, such as Caenorhabditis elegans, are faced with a similar dilemma, as they live in microorganism-rich habitats and eat bacteria as their source of nutrition. Nematodes lost canonical mechanisms of pattern recognition during their evolution and have instead evolved mechanisms to identify specific ligands or symptoms in the host that indicate active infection with an infectious microorganism. Here we review how C. elegans surveys for these patterns of pathogenesis to activate innate immune defences. Collectively, this work demonstrates that using C. elegans as an experimental platform to study host–pathogen interactions at barrier surfaces reveals primordial and fundamentally important principles of innate immune sensing in the animal branch of the tree of life.

Asthma and chronic rhinosinusitis (CRS) are common chronic inflammatory diseases of the respiratory tract that have increased in prevalence over the past five decades. The clinical relationship between asthma and CRS has been well recognized, suggesting a common pathogenesis between these diseases. Both diseases are driven by complex airway epithelial cell and immune cell interactions that occur in response to environmental triggers such as allergens, microorganisms and irritants. Advances, including a growing understanding of the biology of the cells involved in the disease, the application of multiomics technologies and the performance of large-scale clinical studies, have led to a better understanding of the pathophysiology and heterogeneity of asthma and CRS. This research has promoted the concept that these diseases consist of several endotypes, in which airway epithelial cells, innate lymphoid cells, T cells, B cells, granulocytes and their mediators are distinctly involved in the immunopathology. Identification of the disease heterogeneity and immunological markers has also greatly improved the protocols for biologic therapies and the clinical outcomes in certain subsets of patients. However, many clinical and research questions remain. In this Review, we discuss recent advances in characterizing the immunological mechanisms of asthma and CRS, with a focus on the main cell types and molecules involved in these diseases.

CD8⁺ T cells that are repeatedly exposed to antigenic stimulation, such as in the context of progressing neoplasms and chronic viral infections, acquire a dysfunctional or hypofunctional state that is generally known as exhaustion. There have been considerable efforts to develop therapeutic strategies that prevent exhaustion in these pathological scenarios, but there has been limited success. This may be because exhaustion is not the only source of T cell hypofunction in cancer and chronic viral infection. Here, we discuss the molecular and spatiotemporal mechanisms beyond exhaustion that underlie the inability of CD8⁺ T cells to eradicate malignant or chronically infected cells. We also propose a framework to enhance our understanding of these mechanisms — which include tolerization, anergy, senescence, cell death, exclusion and ignorance — with the ultimate aim of informing novel approaches to improve the clinical management of cancer and chronic viral infection.