ABSTRACT
There is increasing evidence that lung-resident memory T and B cells play a critical role in protecting against respiratory reinfection. With a unique transcriptional and phenotypic profile, resident memory lymphocytes are maintained in a quiescent state, constantly surveying the lung for microbial intruders. Upon reactivation with cognate antigen, these cells provide rapid effector function to enhance immunity and prevent infection. Immunization strategies designed to induce their formation, alongside novel techniques enabling their detection, have the potential to accelerate and transform vaccine development. Despite most data originating from murine studies, this review will discuss recent insights into the generation, maintenance and characterisation of pulmonary resident memory lymphocytes in the context of respiratory infection and vaccination using recent findings from human and non-human primate studies.
Subject(s)
Bacterial Infections/prevention & control , Immunologic Memory , Lung/immunology , Memory B Cells/immunology , Memory T Cells/immunology , Respiratory Tract Infections/immunology , Virus Diseases/prevention & control , Animals , Bacterial Infections/immunology , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Bacterial Vaccines/administration & dosage , Bacterial Vaccines/immunology , Host-Pathogen Interactions , Humans , Lung/metabolism , Lung/microbiology , Lung/virology , Memory B Cells/metabolism , Memory B Cells/microbiology , Memory B Cells/virology , Memory T Cells/metabolism , Memory T Cells/microbiology , Memory T Cells/virology , Phenotype , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , Vaccination , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Virus Diseases/immunology , Virus Diseases/metabolism , Virus Diseases/microbiologyABSTRACT
Altered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS). However, the immunomodulatory actions of SCFAs and intermediaries in their ability to influence MS pathogenesis are uncertain. In this study, levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood samples taken at first presentation of Clinically Isolated Syndrome (CIS; an early form of MS) or MS and compared to healthy controls. There was a small but significant reduction in propionate levels in the serum of patients with CIS or MS compared with healthy controls. The frequencies of circulating T follicular regulatory cells and T follicular helper cells were significantly positively correlated with serum levels of propionate. Levels of butyrate associated positively with frequencies of IL-10-producing B-cells and negatively with frequencies of class-switched memory B-cells. TNF production by polyclonally-activated B-cells correlated negatively with acetate levels. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS.
