Volume 20 Issue 5, May 2019

The N⁶-methyladenosine (m⁶A) RNA-modification pathway affects numerous aspects of immune responses. A new study now demonstrates that m⁶A modification of transcripts encoding lysosomal proteases limits the efficiency of tumor-antigen cross-presentation.

The transcription factor PU.1 is not needed for the maintenance of neutrophil identity but is essential for the prevention of excessive tissue damage due to a prolonged immune response. PU.1 restrains the activation of neutrophils by antagonizing the AP-1 transcription factor JunB.

The mechanisms by which the cytokine IFN-λ regulates adaptive immune responses are poorly understood. A new study now reveals a novel IFN-λ-mediated signal-transmission system that enhances immunity after infection of the mouse respiratory tract with influenza virus.

The cytokine IL-17 augments metabolism in fibroblastic reticular cells in lymph nodes, which enhances their proliferation and survival to support B cell responses during autoimmunity.

Comprehensive immunity requires that cells sense intracellular pathogens. In their Review, Shao and colleagues describe mechanisms for the recognition of intracellular lipopolysaccharide and its essential role in responses to Gram-negative bacteria.

Fibroblastic reticular cells support lymph-node function and adaptive immunity. McGeachy and colleagues show that the cytokine IL-17 is needed to trigger metabolic changes required for the proliferation and survival of these cells in reactive lymph nodes.

Neutrophils rapidly respond to bacterial and fungal infections but can cause substantial collateral tissue damage if not restrained. Rosenbauer and colleagues show that the transcription factor PU.1 serves a cell-intrinsic role to prevent over-exuberant neutrophil responses to fungal infection.

Innate immunity protects the central nervous system against fungal pathogens. Lionakis and colleagues identify Candidalysin, a Candida virulence factor that elicits microglial expression of the cytokine IL-1β and chemokine CXCL1 and facilitates neutrophil recruitment. Alteration of this pathway impairs antifungal responses.

Control of macrophage activation in the lungs is essential for the prevention of tissue damage. MacDonald and colleagues show that alveolar macrophages have impaired glycolysis and are hyporesponsive during type 2 inflammation in a manner controlled by the lung environment.

Succinate is a signaling metabolite sensed extracellularly by SUNCR1. Fernandez-Veledo and colleagues show that activation of SUCNR1 promotes an anti-inflammatory phenotype in adipose-tissue macrophages in lean mice and people.

The role of IFN-λ in adaptive immunity is not well characterized. Staeheli and colleagues show that in the lungs, IFN-λ elicits production of the cytokine TSLP from M cells and that this in turn is essential for effective adaptive immunity and control of infection with influenza virus.

Lymph fluid carries cells, debris and viruses to draining lymph nodes. Hickman and colleagues show that large viruses can enter lymph node conduits and gain access to dendritic cells positioned deep within lymph nodes for efficient presentation of antigen to CD8⁺ T cells.

Cross-protective responses across all strains of influenza virus (IAV, IBV and ICV) are a key goal of universal vaccines against influenza. Kedzierska and colleagues identify cytotoxic T cells present in blood and lungs of healthy people that are directed against all strains of influenza virus.

Muscle damage elicits a sterile immune response that facilitates complete regeneration. Nagy and colleagues map the mediator lipidome during the transition from inflammation to resolution in skeletal muscle injury.

Respiratory infections are the principal cause of asthma exacerbations in children. Altman and colleagues use a systems approach to describe the pathways associated with asthma exacerbations in a cohort of inner-city children.

Determining TCR specificity represents a formidable technical barrier to the harnessing of T cell function. Kisielow and colleagues describe a novel platform for efficient determination of TCR specificities in a variety of infectious and cancer settings and in both human systems and mouse systems.