Frequency of CXCR3 CD8 T-Lymphocyte Subsets in Peripheral Blood Is Associated With the Risk of Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome Development in Advanced HIV Disease.

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a clinical aggravation of TB symptoms observed among a fraction of HIV coinfected patients shortly after the start of antiretroviral therapy (ART). Of note, TB-IRIS is characterized by exacerbated inflammation and tissue damage that occurs in response to the elevated production of CD4 T cell-derived IFN-γ. Nevertheless, the possible participation of CD8 T cells in TB-IRIS development remains unclear.

Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV.

Most persons living with HIV (PLWH) experience a significant restoration of their immunity associated with successful inhibition of viral replication after antiretroviral therapy (ART) initiation. Nevertheless, with the robust quantitative and qualitative restoration of CD4 T-lymphocytes, a fraction of patients co-infected with tuberculosis develop immune reconstitution inflammatory syndrome (TB-IRIS), a dysregulated inflammatory response that can be associated with significant tissue damage. Several studies underscored the role of adaptive immune cells in IRIS pathogenesis, but to what degree T lymphocyte activation contributes to TB-IRIS development remains largely elusive.

Toxoplasma gondii-Induced Neutrophil Extracellular Traps Amplify the Innate and Adaptive Response.

Toxoplasmosis affects one-third of the human population worldwide. Humans are accidental hosts and are infected after consumption of undercooked meat and water contaminated with Toxoplasma gondii cysts and oocysts, respectively. Neutrophils have been shown to participate in the control of T.

Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria.

Background: Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated.

Objective: To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients.

Methods: Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P.

Increased frequencies of circulating CCR5 memory T cells are correlated to chronic chagasic cardiomyopathy progression.

The infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease, a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagasic cardiomyopathy (CCC), a progressive inflammatory and fibrosing disease, is the most prominent clinical form of Chagas disease, culminating in heart failure and high rates of sudden death. CCC pathogenesis is influenced by both host and parasite factors and is proposed to be mostly immune-driven.

Plasmodium vivax Infection Impairs Regulatory T-Cell Suppressive Function During Acute Malaria.

The balance between pro- and antiinflammatory mechanisms is essential to limit immune-mediated pathology, and CD4+ forkhead box P3 (Foxp3+) regulatory T cells (Treg) play an important role in this process. The expression of inhibitory receptors regulates cytokine production by Plasmodium vivax-specific T cells. Our goal was to assess the induction of programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen (CTLA-4) on Treg during malaria and to evaluate their function.

Human T Lymphocytes Are Permissive for Dengue Virus Replication.

Dengue virus (DV) infection can cause either a self-limiting flu-like disease or a threatening hemorrhage that may evolve to shock and death. A variety of cell types, such as dendritic cells, monocytes, and B cells, can be infected by DV. However, despite the role of T lymphocytes in the control of DV replication, there remains a paucity of information on possible DV-T cell interactions during the disease course.

Induction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production.

The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T-lymphocyte attenuator-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and programmed death-1 (PD-1) are involved in the functional impairment of T cells during infection.

The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.

Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria.

Selective expansion of polyfunctional pathogen-specific CD4(+) T cells in HIV-1-infected patients with immune reconstitution inflammatory syndrome.

Since the introduction of highly active antiretroviral therapies (ART), the prognosis for HIV-1 patients has improved immensely. However, approximately 25% of patients can experience a variety of inflammatory symptoms that are collectively known as immune reconstitution inflammatory syndrome (IRIS). Studying the etiology and immunopathology of IRIS has been hampered by the fact that the symptoms and associated opportunistic infections are highly varied.

IL-10 limits parasite burden and protects against fatal myocarditis in a mouse model of Trypanosoma cruzi infection.

Chagas' disease is a zoonosis prevalent in Latin America that is caused by the protozoan Trypanosoma cruzi. The immunopathogenesis of cardiomyopathy, the main clinical problem in Chagas' disease, has been extensively studied but is still poorly understood. In this study, we systematically compared clinical, microbiologic, pathologic, immunologic, and molecular parameters in two mouse models with opposite susceptibility to acute myocarditis caused by the myotropic Colombiana strain of T.

Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing immune reconstitution inflammatory syndrome.

Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in the treatment of HIV-infected patients. To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of antiretroviral therapy. Patients developing IRIS episodes displayed higher frequencies of effector memory, PD-1(+), HLA-DR(+), and Ki67(+) CD4(+) T cells than patients without IRIS.

Th1-driven immune reconstitution disease in Mycobacterium avium-infected mice.

Following antiretroviral therapy, a significant proportion of HIV(+) patients with mycobacterial coinfections develop a paradoxical, poorly understood inflammatory disease termed immune reconstitution inflammatory syndrome (IRIS). Here, we show that Mycobacterium avium-infected T cell-deficient mice injected with CD4 T cells also develop an immune reconstitution disease (IRD) manifesting as weight loss, impaired lung function, and rapid mortality. This form of IRD requires Ag recognition and interferonγ production by the donor CD4 T cells and correlates with marked alterations in blood and tissue CD11b(+) myeloid cells.

Intranasal Poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte/macrophage population.

Type I IFN has been demonstrated to have major regulatory effects on the outcome of bacterial infections. To assess the effects of exogenously induced type I IFN on the outcome of Mycobacterium tuberculosis infection, we treated pathogen-exposed mice intranasally with polyinosinic-polycytidylic acid condensed with poly-l-lysine and carboxymethylcellulose (Poly-ICLC), an agent designed to stimulate prolonged, high-level production of type I IFN. Drug-treated, M.

In situ IL-12/23p40 production during mycobacterial infection is sustained by CD11bhigh dendritic cells localized in tissue sites distinct from those harboring bacilli.

Although IL-12/23p40 is known to play a major role in host resistance to Mycobacterium spp, the cellular source, tissue localization, and regulation of p40 production during mycobacterial infection in vivo has been unclear. In this study, we used IL-12/23p40eYFP (yet40) reporter mice to track expression of the cytokine following Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. We found that in spleens of these mice, p40 production is initiated by a transient burst from CD11b(low)CD11c(+) dendritic cells (DC) which are later replaced at the onset of granuloma formation by CD11b(high)CD11c(+) DC as the major source of the cytokine.

Immunoregulatory mechanisms and CD4-CD8- (double negative) T cell subpopulations in human cutaneous leishmaniasis: a balancing act between protection and pathology.

Cellular immune responses directed against protozoan parasites are key for controlling pathogen replication and disease resolution. However, an uncontrolled, or improperly controlled, response can be deleterious to the host in terms of both allowing for the establishment of pathology, as well as less effective establishment of memory responses. Human cutaneous leishmaniasis is a disease caused by the infection with Leishmania spp.

Disparate immunoregulatory potentials for double-negative (CD4- CD8-) alpha beta and gamma delta T cells from human patients with cutaneous leishmaniasis.

Although most T lymphocytes express the alphabeta T-cell receptor and either CD4 or CD8 molecules, a small population of cells lacking these coreceptors, CD4- CD8- (double negative [DN]) T cells, has been identified in the peripheral immune system of mice and humans. To better understand the role that this population may have in the human immune response against Leishmania spp., a detailed study defining the activation state, cytokine profile, and the heterogeneity of DN T cells bearing alphabeta or gammadelta T-cell receptors was performed with a group of well-defined cutaneous leishmaniasis patients.

Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis.

Leishmaniasis is an important parasitic disease affecting millions worldwide. In attempts to understand the clinical relevance of immunological measurements as determined using flow cytometry, several immunological phenotypes were determined for a group of well defined human leishmaniasis patients and correlated with clinical measurements of the disease (Montenegro skin test (MST) and lesion area). The analysis demonstrated a positive correlation between the MST size and the frequency of ex vivo recent activated CD4(+) T cells.

Norepinephrine, dopamine and dexamethasone modulate discrete leukocyte subpopulations and cytokine profiles from human PBMC.

The interplay between the immune and neuroendocrine systems is intense, with the cross-talk between these two systems increasing during stress circumstances. Stress events culminate with hormonal pathway activation elevating the plasma levels of glucocorticoids and catecholamines. The majority of the works evaluating the effects of stress hormones on immune cells have utilized in vivo animal models or clinical studies.

Insights into CD4+ memory T cells following Leishmania infection.

Recent publications by Zaph et al. have highlighted the distinct requirements for generating and maintaining different subpopulations of CD4(+) memory T cells after infection with Leishmania major in mice. These studies have advanced the understanding of the nature of long-lasting immunity to Leishmania and, when considered within the context of previous work on both murine and human leishmaniasis, will aid the design of effective vaccines.

Cure of innate intestinal immune pathology by CD4+CD25+ regulatory T cells.

CD4+CD25+ regulatory T (T(R)) cells are a naturally occurring population of T cells that suppress the development of a variety of pathological immune responses. However, as human inflammatory diseases are usually not diagnosed until after the onset of clinical symptoms, it is of great interest to determine whether CD4+CD25+ T(R) cells can reverse established pathology. To examine this question we have utilized a murine model of human inflammatory bowel disease (IBD), where pathology is triggered by infection of immune deficient RAG-/- mice with the pathogenic bacterium Helicobacter hepaticus.