Radiation exposure induces cell and tissue damage causing local and systemic inflammatory responses. Since the inflammasome pathway is triggered by cell death and danger-associated molecular patterns (DAMPs), we hypothesized that the inflammasome may signal acute and chronic immune responses to radiation. Using a mouse radiation model, we show that radiation induces a dose-dependent increase in inflammasome activation in macrophages, dendritic cells, NK cells, T cells, and B cells as judged by cleaved caspase 1 detection in cells. Time course analysis showed the appearance of cleaved caspase 1 in cells by day 1 and sustained expression until day 7 post-radiation. Also, cells showing inflammasome activation co-expressed the cell-surface apoptosis marker, Annexin V. The role of caspase 1 as a trigger for hematopoietic cell losses after radiation was studied in caspase 1 −/− mice. We found less radiation-induced cell apoptosis and immune cell loss in caspase 1 −/− mice than control mice. Next, we tested whether uric acid might mediate inflammasome activation in cells by treating mice with allopurinol and discovered that allopurinol treatment completely blocked caspase 1 activation in cells. Finally, we demonstrate that radiation-induced caspase 1 activation occurs by a Nod-like receptor family protein 3 (NLRP3) independent mechanism since radiation-exposed Nlrp3 −/− mice showed caspase 1 activation profiles that were indistinguishable from wild-type mice. In summary, our data demonstrate that inflammasome activation occurs in many immune cell types following radiation exposure and that allopurinol prevented radiation-induced inflammasome activation. These results suggest that targeting the inflammasome may help control radiation-induced inflammation.

Purpose Selection of the correct femoral stem size is crucial in total hip arthroplasty for an uncomplicated implantation and good initial stability. Pre-operative templating has been shown to be a valuable tool in predicting the correct implant size. For short-stem total hip arthroplasty (SHA), which recently is increasingly used, it is unknown if templating can be performed as reliable as conventional total hip arthroplasty (THA). Methods A total of 100 hip arthroplasties, 50 with SHA and 50 with THA, were templated by four orthopaedic surgeons each. The surgeons had different levels of professional experience and performed a digital template of the acetabular and femoral component on the pre-operative radiographs. The results were compared with the truly inserted implant size. Results For the femoral stems the average percentage of agreement (±1 size) was 89.0 % in SHA and 88.5 % in THA. There was no significant difference among surgeons in the accuracy of templating the correct stem size and no significant difference between templating SHA and THA. For the acetabular component the average percentage of agreement (±1 size) was 75.8 %. However, the more experienced surgeons showed a significant higher accuracy for templating the correct cup size than the less experienced surgeons. Conclusion Digital templating of SHA can predict the stem sizes as accurately as conventional THA. Therefore digital templating is also recommendable for SHA, as it helps to predict the implant size prior to surgery and thereby might help to avoid complications.

T cell receptor γδ cells are known to be the primary effector T cells involved in the response to bacterial infections, yet their phenotypic characteristics are not as well established as other T cell subsets. In this study, we used cytometry by time-of-flight mass cytometry to better characterize the phenotypic response of T cell receptor γδ cells to Streptococcus pneumoniae lung infection. Mice were infected, and cells from lung washouts, spleen, and lymph nodes were stained to detect cell-surface, intracellular, and signaling markers. We observed that infection caused a significant increase in T cell receptor γδ cells, which expressed high interferon-γ and interleukin-17A levels. Profiling T cell receptor γδ cells by cytometry by time-of-flight revealed that activated γδ T cells uniquely coexpressed cell-surface Gr-1, cluster of differentiation 14, and cluster of differentiation 274 (programmed death-ligand 1). Further classification of Gr-1 expression patterns on T cell receptor γδ cells demonstrated that Gr-1(+) T cell receptor γδ cells were the primary source of interferon-γ, whereas Gr-1(-) cells mostly expressed interleukin-17A. Gr-1(+) T cell receptor γδ cells also showed higher ζ-chain-associated protein kinase 70, p38, and 4eBP1 signaling in response to infection as compared with Gr-1(-) T cell receptor γδ cells. Taken together, Gr-1 expression patterns on γδ T cells in the lung provide a robust marker to differentiate interferon-γ- and interleukin-17A-producing subsets involved in the early immune response to bacterial pneumonia.