Immunology

eLife assessment

This manuscript provides an important advance in our understanding of burn-associated T-cell responses. The evidence is convincing and the techniques are using the latest single-cell RNA-seq approaches in a rigorous manner. The studies are done directly on human skin so are highly clinically relevant.

eLife assessment

This landmark study uses compelling approaches such as quantitative and screening mass spectrometry to identify peptides from tuberculosis bacteria that are presented by macrophages infected with this pathogen. The authors provide convincing evidence that the presentation of these antigens depends on a specialist bacterial secretion system. The study will be of interest to infectious disease specialists and of particular value for future vaccine development.

eLife assessment

The present study presents the important finding that HIV infection activates the NLRP3, IFI16, and AIM 2 inflammasome pathways and that treatment with the anti-caspase 1 inhibitor VX-765 moderately reduces inflammasome activation and CD4 T cell depletion in a humanized NSG mouse model. The evidence supporting that inflammasome activation may play an important role in CD4 T cell depletion and that anti-caspase-1 inhibitors may reduce harmful inflammation is for the most part solid, although not always complete. The results will be of interest to scientists and physicians working on HIV immunology, pathogenesis and cure strategies.

eLife assessment

This paper reports important findings on the mechanisms by which death pathways are activated by Shigella infection to impact the host response. The methods used provide compelling evidence for the involvement of multiple death cell pathways in the pathogenesis and host response to murine shigellosis. The results presented therein will be of interest to investigators in the field of bacterial pathogenesis, infectious disease and immunology.

eLife assessment

Humanized transgenic mice represent an important tool for antibody discovery and vaccine profiling but their similarity to human immune responses has not been established so far. In this manuscript, Richardson et al. comprehensively characterize IgH repertoires of Ky mice that carry human immunoglobulin heavy (IgH) and light chain (Igk and l) genes. The data presented here will be useful for setting a foundation for the use of this model, as well as other similar transgenic models, in future studies.

eLife assessment

The effect of helminth infection on vaccination against tuberculosis infection and disease is an important area of study. In this manuscript, the authors build off of a large body of prior data showing that mycobacterial antigens upregulate MINCLE whilst the cytokine IL-4 downregulates MINCLE. As IL-4 is upregulated during Helminth infections, this can antagonize Th1/Th17 responses. By using two different models of helminth infection, the authors demonstrate an organ-specific impairment of Th17 responses in a vaccination setting with a MINCLE-dependent adjuvant. The work is topical and may have important translational implications for patients with tuberculosis and helminth co-infections and/or vaccination regimens for patients with helminth infections. The study will be of interest to individuals studying the convergence of different infectious diseases.

eLife assessment

Host directed therapies (HDTs) have the potential to improve management of tuberculosis (TB) through shortening of the duration of standard 6-month chemotherapy and promoting recovery of respiratory sufficiency. Several such agents have come to the fore recently and in this study, the authors investigate the use of sertraline (SRT) and demonstrate that it potentiates the activity of anti-tubercular drugs in macrophages as well as in the murine model of TB infection. The authors propose a model whereby SRT acts through modulation of the inflammasome.

eLife assessment

The authors present valuable findings about the mechanisms inducing IL-10 production by B cells in neonates. The evidence supporting the claims of the authors is solid, although the manuscript would be strengthened by amendments to the presentation of the data and explanation of some experimental choices.

eLife assessment

The enrichment of Tfh17 cells in Tfh cell central memory compartment and the dominance of Tfh17 cell population and the Tfh17 transcriptional signature in circulating Tfh cells at the memory phase are nicely demonstrated, and may well be helpful for understanding the heterogeneity of memory Tfh cells and potentially providing clues for vaccine design. The in vitro differentiation system for mouse Tfh cells also provides a strategy for others to build upon in dissection of Tfh cell development and function.

eLife assessment

The authors demonstrate that patients with obesity-associated osteoarthritis and mice with the ApoE gene deficiency showed phenotypes of synovitis and enhanced macrophage infiltration in synovial tissues. Overall, this potentially important study is well-designed and carefully executed, although additional evidence is needed to fully support the authors' conclusions.