Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis

Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Castellanos et al. show a protective role for microbial induction of the IBD-linked protein TL1A in promoting ILC3 barrier immunity and uncover a pathogenic role for TL1A-induced expression of OX40L on ILC3s in driving chronic T cell colitis.

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Salmonella Persist in Activated Macrophages in T Cell-Sparse Granulomas but Are Contained by Surrounding CXCR3 Ligand-Positioned Th1 Cells

The pathogen Salmonella enterica (Se) can paradoxically persist in hosts while being controlled by IFN-γ-producing Th1 cells. Goldberg et al. show that the bacteria survive by resisting the effects of toxic host molecules in myeloid cells within granulomas, in areas lacking T cells. Infection is constrained by Th1 cells positioned around the granuloma via the CXCR3-CXCL9/10 chemokine axis.

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Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier

Understanding how HIV-1 VRC01-class broadly neutralizing antibodies overcome maturation barriers is key for vaccine development. Bonsignori et al. inferred the unmutated common ancestor of the VRC01 lineage, reconstructed the stages of lineage maturation, and identified multiple solutions adopted by evolving B cells to overcome the N276 glycan barrier and achieve broad neutralization.

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Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance

Serrated adenocarcinomas are an aggressive and treatment-resistant form of colorectal cancer. Nakanishi et al. show that expression of atypical PKCs is reduced in human serrated tumors and that their loss results in spontaneous serrated tumorigenesis with stromal activation and immunosuppression in mice. The simultaneous inhibition of stromal activation combined with anti-PD-L1 showed synergistic therapeutic potential.

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Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12

Anti-PD-1 mAbs can induce sustained clinical responses in cancer but how they function in vivo remains incompletely understood. Garris et al. show that effective anti-PD-1 immunotherapy requires intratumoral dendritic cells (DCs) producing IL-12. Anti-PD-1 indirectly activates DCs through IFN-γ released from drug-activated T cells. Furthermore, agonizing the non-canonical NF-κB pathway activates DCs and enhances aPD-1 therapy in an IL-12-dependent manner.

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Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

Vaccine-induced immunity to HIV is a major research focus, but relevant correlates of protection remain controversial. Here, Pauthner et al. study protection from hard-to-neutralize SHIVBG505 challenge after immunization with native-like BG505 Envelope trimers in nonhuman primates and identify neutralizing antibodies, but not T cell or ADCC activity, as correlates of protection.

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Impact of individualized target mean arterial pressure for septic shock resuscitation on the incidence of acute kidney injury: a retrospective cohort study

To examine the relationship between delta mean arterial pressure (ΔMAP; MAP change between pre-admission minus post-resuscitation) and acute kidney injury (AKI) among patients with septic shock. In this retros...

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