Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses

Bacterial phagocytosis and antigen cross-presentation to activate CD8+ T cells are principal functions of professional antigen presenting cells. However, conventional CD4+ T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8+ T cells, which proliferate and become cytotoxic in response. CD4+ T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8+ T cells with low PD-1 expression. Moreover, transphagocytic CD4+ T cells induce protective anti-tumour immune responses by priming CD8+ T cells, highlighting the potential of CD4+ T cells as a tool for cancer immunotherapy.J.M.G.-G. is supported by the Miguel Servet Program (Instituto de Salud Carlos III; ISCIII) and V.Z. by the ISCIII. This work was supported by grants from the Spanish Ministries of Science and Technology (MICINN; BFU2011-29450 to E.V.) and of Economy and Competitiveness (MINECO; SAF201456716-REDT and BFU2014-59585-R to E.V., SAF2014-55579-R to F.S.M., SAF201347975-R to B.A., SAF2014-58895-JIN to A.C.-A.), the ISCIII (PI14/00526; CP11/00145; CPII16/00022 to J.M.G.-G.), the Fundación Ramón Areces (to J.M.G.-G.), the Madrid regional government (INDISNET-S2011/BMD-2332 to F.S.M.) and the European Research Council (ERC-2011-AdG 294340-GENTRIS to F.S.M.; ERC 2013-AdG 334763 NOVARIPP to B.A.). F.S.M. and J.M.G.-G. are also financed by CIBER Cardiovascular, Spain.S

CD69 modulates sphingosine-1-phosphate-induced migration of skin dendritic cells

In this study, we have investigated the role of CD69, an early inducible leukocyte activation receptor, in murine dendritic cell (DC) differentiation, maturation, and migration. Skin DCs and DC subsets present in mouse lymphoid organs express CD69 in response to maturation stimuli. Using a contact sensitization model, we show that skin DCs migrated more efficiently to draining lymph nodes (LNs) in the absence of CD69. This was confirmed by subcutaneous transfer of CD69-/- DCs, which presented an increased migration to peripheral LNs. Two-photon microscopy analysis showed that once DCs reached the LNs, CD69 deficiency did not alter DC interstitial motility in the LNs. Chemotaxis to sphingosine-1-phosphate (S1P) was enhanced in CD69-/- DCs compared with wild-type DCs. Accordingly, we detected a higher expression of S1P receptor type-1 (S1P(1)) by CD69-/- DCs, whereas S1P(3) expression levels were similar in wild-type and CD69-/- DCs. Moreover, in vivo treatment with S1P analogs SEW2871 and FTY720 during skin sensitization reduced skin DC migration to peripheral LNs. These results suggest that CD69 regulates S1P-induced skin DC migration by modulating S1P(1) function. Together, our findings increase our knowledge on DC trafficking patterns in the skin, enabling the development of new directed therapies using DCs for antigen (Ag) delivery

Maternal distress and the development of hypertensive disorders of pregnancy

Despite the implementation of programmes to improve maternal health, maternal and foetal mortality rates still remain high. The presence of maternal distress and its association with the development of pregnancy hypertensive disorders is not well established. The aim of this study was to evaluate the association between maternal distress and the development of hypertensive disorders in pregnancy in a prospective cohort of 321 Mexican women. Symptoms of maternal distressing were evaluated at week 20th of gestation using the General Health Questionnaire. The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the odds of developing a pregnancy hypertensive disorder by 5.1–26.4 times in study population (p values < .05). Our results support the participation of maternal distress in the development of hypertensive disorders of pregnancy. The implementation of effective programmes prioritising risk factors during pregnancy including the presence of maternal distressing factors is recommended.Impact statement What is already known on this subject: Changes in the nervous, endocrine, and immune systems have been observed in pregnant women with distress conditions leading to gestational disorders. What do the results of this study add: The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the developing of hypertensive disorders in Mexican population. What are the implications of these findings for clinical practice and/or further research: These findings may contribute to a better understanding of the role of the maternal stress in the development of hypertensive disorders of pregnancy, and in the implementation of effective programmes for clinical practice prioritising risk factors during pregnancy, including the presence of maternal distressing factors