Volume 21 Issue 6, June 2020

A new study reports that T_H2-coordinated tissue repair takes precedence over long-term protective immunity in urinary tract infections. Although effective in the interim, this can lead to recurrent infections and bladder dysfunction.

B cells undergo iterative rounds of somatic hypermutation and selection for high-affinity antigen binding in the germinal center microenvironment. Two new studies provide insights into the temporal and spatial control mechanisms that act within B cells and follicular dendritic cells to jointly govern B cell differentiation and cell traffic within the GC.

Injury or infection renders patients vulnerable to secondary pneumonia. A new study indicates that SIRP-α triggers prolonged impairment of the phagocytic capacity of alveolar macrophages after the resolution of primary bacterial or viral pneumonia.

Tsokos reviews how the genetic, epigenetic and microbial environments influence innate and adaptive immune cells to drive immunopathology and organ damage in systemic lupus erythematosus.

Human aging is characterized by an elevated basal inflammatory state. Gilroy and colleagues use a tractable in vivo human inflammation model to demonstrate a mechanism whereby efferocytosis is impaired in the elderly but is reversible by p38 inhibition.

NLRP6 is highly expressed in the gut; however, persistent NLRP6 activation can lead to excessive IL-18 production and intestinal bowel disease. Venuprasad and colleagues identify the K63-linked ubiquitin deubiquitinase Cyld as a negative regulator of NLRP6.

Sepsis and physical trauma can increase the susceptibility of patients to pneumonia. Roquilly and colleagues demonstrate that sepsis results in durable impairment of alveolar phagocytic function that is dependent on the localized expression of the inhibitory receptor SIRPα.

Ludewig and colleagues use fate-mapping reporter cells, single-cell RNA-seq analysis and high-resolution microscopy to identify and track the spatial reorganization of follicular reticular cells within germinal centers during the course of an immune response.

Germinal centers are typically divided into dark and light zones. Clark and colleagues identify ‘gray zone’ cyclin B1⁺ B cell clusters as sites of ongoing cell proliferation, and these cells are distinct from dark zone B cells that undergo AID-dependent somatic hypermutation. This separation of function safeguards B cells undergoing DNA replication against potential mutagenic events that could result in neoplastic transformation.

Abraham and colleagues show that a highly polarized T_H2 bladder response to urinary tract infections promotes epithelial repair at the expense of preventing new infections and associated bladder dysfunction.

Akbar and colleagues show that sestrins induce the reprogramming of non-proliferative, senescent-like CD27^–CD28^–CD8⁺ T cells to acquire an innate-like killing activity modulated by the NK receptor NKG2D and the adaptor molecule DAP12.