Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency.

Tissue-resident memory T (T) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common T cell fate remains poorly understood. Here, we show that whereas skin T cells strictly require transforming growth factor β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β to drive T cells in the small intestine.

Antifungal potential, mechanism of action, and toxicity of 1,4-naphthoquinone derivatives.

Background: The rising prevalence of fungal infections and challenges such as adverse effects and resistance against existing antifungal agents have driven the exploration of new antifungal substances.

Methods: We specifically investigated naphthoquinones, known for their broad biological activities and promising antifungal capabilities. It specifically examined the effects of a particular naphthoquinone on the cellular components of Candida albicans ATCC 60193.

Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation.

The memory CD8 T cell pool contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. Here, we examined the epigenetic landscape of CD8 T cells isolated from seven non-lymphoid organs across four distinct infection models, alongside their circulating T cell counterparts. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), we found that tissue-resident memory T (T) cells and circulating memory T (T) cells develop along distinct epigenetic trajectories.

Single-cell protein expression profiling resolves circulating and resident memory T cell diversity across tissues and infection contexts.

Memory CD8 T cells can be broadly divided into circulating (T) and tissue-resident memory T (T) populations. Despite well-defined migratory and transcriptional differences, the phenotypic and functional delineation of T and T cells, particularly across tissues, remains elusive. Here, we utilized an antibody screening platform and machine learning prediction pipeline (InfinityFlow) to profile >200 proteins in T and T cells in solid organs and barrier locations.

Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes.

Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells.

Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity.

Tissue-resident memory T (T) cells are non-recirculating cells that exist throughout the body. Although T cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze T cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate T cell function, durability and malleability.

Developmental plasticity allows outside-in immune responses by resident memory T cells.

Central memory T (T) cells patrol lymph nodes and perform conventional memory responses on restimulation: proliferation, migration and differentiation into diverse T cell subsets while also self-renewing. Resident memory T (T) cells are parked within single organs, share properties with terminal effectors and contribute to rapid host protection. We observed that reactivated T cells rejoined the circulating pool.

Trends Associated with Stillbirth in a Maternity Hospital School in the North Zone of São Paulo: A Cross-Sectional Study.

Objective:  To evaluate conditions associated with stillbirth (SB), and possible trends related with it, in a maternity hospital school in the North zone of São Paulo.

Methods:  An observational, cross-sectional study conducted at the Hospital Maternidade-escola de Vila Nova Cachoeirinha with 1,139 SBs in the period of 2003 to 2017. Cases of intermediate SB (ISB) (weight between 500 and 999 g) and late SB (LSB) (weight ≥ 1,000 g) were compared.

MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control.

Cardiomyopathy is the most serious consequence of Chagas disease, a neglected human disorder caused by Trypanosoma cruzi infection. Because T. cruzi parasites invade cardiomyocytes, we sought to investigate whether these cells recognize the parasite in vivo by receptors signaling through the MyD88 adaptor, which mediates the activation pathway of most Toll-like receptors (TLRs) and IL-1/IL-18 receptors, and influence the development of acute cardiac pathology.

The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8 T cells.

Extracellular ATP (eATP) is an ancient 'danger signal' used by eukaryotes to detect cellular damage. In mice and humans, the release of eATP during inflammation or injury stimulates both innate immune activation and chronic pain through the purinergic receptor P2RX7. It is unclear, however, whether this pathway influences the generation of immunological memory, a hallmark of the adaptive immune system that constitutes the basis of vaccines and protective immunity against re-infection.

Programmed Cell Death Protein 1-PDL1 Interaction Prevents Heart Damage in Chronic Infection.

Chagas disease is a neglected parasitic infection that affects around six to seven million people, mainly in Latin America. About 30-35% of infected people present chronic Chagas cardiomyopathy (CCC), which eventually leads to death. This condition is characterized by local parasite persistence and leukocyte infiltration.

Intravital mucosal imaging of CD8 resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory.

CD8 T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Here we used two-photon intravital microscopy to visualize the responses of CD8 resident memory T cells (T cells) within the reproductive tracts of live female mice. We found that mucosal T cells were highly motile, but paused and underwent in situ division after local antigen challenge.

IFN-γ Priming Effects on the Maintenance of Effector Memory CD4(+) T Cells and on Phagocyte Function: Evidences from Infectious Diseases.

Although it has been established that effector memory CD4(+) T cells play an important role in the protective immunity against chronic infections, little is known about the exact mechanisms responsible for their functioning and maintenance, as well as their effects on innate immune cells. Here we review recent data on the role of IFN-γ priming as a mechanism affecting both innate immune cells and effector memory CD4(+) T cells. Suboptimal concentrations of IFN-γ are seemingly crucial for the optimization of innate immune cell functions (including phagocytosis and destruction of reminiscent pathogens), as well as for the survival and functioning of effector memory CD4(+) T cells.

Splenic Macrophage Subsets and Their Function during Blood-Borne Infections.

The spleen is one of the major immunological sites for maintaining blood homeostasis. Previous studies showed that heterogeneous splenic macrophage populations contribute in complimentary ways to control blood-borne infections and induce effective immune responses. Marginal metallophilic macrophages (MMMΦs) and marginal zone macrophages (MZMΦs) are cells with great ability to internalize blood-borne pathogens such as virus or bacteria.

In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria.

Chagas disease: still many unsolved issues.

Over the past 20 years, the immune effector mechanisms involved in the control of Trypanosoma cruzi, as well as the receptors participating in parasite recognition by cells of the innate immune system, have been largely described. However, the main questions on the physiopathology of Chagas disease remain unanswered: "Why does the host immune system fail to provide sterile immunity?" and "Why do only a proportion of infected individuals develop chronic pathology?" In this review, we describe the mechanisms proposed to explain the inability of the immune system to eradicate the parasite and the elements that allow the development of chronic heart disease. Moreover, we discuss the possibility that the inability of infected cardiomyocytes to sense intracellular T.