Combined immunization using DNA-Sm14 and DNA-Hsp65 increases CD8+ memory T cells, reduces chronic pathology and decreases egg viability during Schistosoma mansoni infection.

BMC Infect Dis

Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av, do Café s/n 14040-903 Ribeirão Preto, São Paulo, Brazil.

Published: May 2014

Background: Schistosomiasis is one of the most important neglected diseases found in developing countries and affects 249 million people worldwide. The development of an efficient vaccination strategy is essential for the control of this disease. Previous work showed partial protection induced by DNA-Sm14 against Schistosoma mansoni infection, whereas DNA-Hsp65 showed immunostimulatory properties against infectious diseases, autoimmune diseases, cancer and antifibrotic properties in an egg-induced granuloma model.

Methods: C57BL/6 mice received 4 doses of DNA-Sm14 (100 μg/dose) and DNA-Hsp65 (100 μg/dose), simultaneously administrated, or DNA-Sm14 alone, once a week, during four weeks. Three groups were included: 1- Control (no immunization); 2- DNA-Sm14; 3- DNA-Sm14/DNA-Hsp65. Two weeks following last immunization, animals were challenged subcutaneously with 30 cercariae. Fifteen, 48 and 69 days after infection splenocytes were collected to evaluate the number of CD8+ memory T cells (CD44(high)CD62(low)) using flow cytometry. Forty-eight days after challenge adult worms were collected by portal veins perfusion and intestines were collected to analyze the intestinal egg viability. Histological, immunohistochemical and soluble quantification of collagen and α-SMA accumulation were performed on the liver.

Results: In the current work, we tested a new vaccination strategy using DNA-Sm14 with DNA-Hsp65 to potentiate the protection against schistosomiasis. Combined vaccination increased the number of CD8+ memory T cells and decreased egg viability on the intestinal wall of infected mice. In addition, simultaneous vaccination with DNA-Sm14/DNA-Hsp65 reduced collagen and α-SMA accumulation during the chronic phase of granuloma formation.

Conclusion: Simultaneous vaccination with DNA-Sm14/DNA-Hsp65 showed an immunostimulatory potential and antifibrotic property that is associated with the reduction of tissue damage on Schistosoma mansoni experimental infection.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031977PMC
http://dx.doi.org/10.1186/1471-2334-14-263DOI Listing

Publication Analysis

Top Keywords

cd8+ memory
12
memory cells
12
egg viability
12
schistosoma mansoni
12
immunization dna-sm14
8
dna-sm14 dna-hsp65
8
mansoni infection
8
vaccination strategy
8
100 μg/dose
8
number cd8+
8

Similar Publications

Maternal gut microbiota composition contributes to the status of the neonatal immune system and could influence the early life higher susceptibility to viral respiratory infections. Using a novel protocol of murine maternal probiotic supplementation, we report that perinatal exposure to () or () increases the influenza A/PR8 virus (IAV) clearance in neonates. Following either supplementation, type 1 conventional dendritic cells (cDC1) were amplified in the lymph nodes leading to an enhanced IAV antigen-experienced IFN-γ producing effector CD8 T cells in neonates and IAV-specific resident memory CD8 T cells in adulthood.

View Article and Find Full Text PDF

We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated.

View Article and Find Full Text PDF

Deep profiling deconstructs features associated with memory CD8 T cell tissue residence.

Immunity

December 2024

Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Tissue-resident memory CD8 T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics.

View Article and Find Full Text PDF

Tocilizumab and immune signatures for targeted management of cytokine release syndrome in immune checkpoint therapy.

Ann Oncol

December 2024

Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Department of Medicine, Immunology and Allergy Service, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. Electronic address:

Background: This study aimed to identify specific biomarkers in oncology patients experiencing immune-related cytokine release syndrome (irCRS)-like symptoms during immune checkpoint inhibitor (ICI) therapy, including severe cases like hemophagocytic lymphohistiocytosis (irHLH), and to distinguish these from sepsis. A secondary objective was to retrospectively analyze the efficacy of tocilizumab (TCZ) in treating corticosteroid (CS)-refractory high-grade irCRS.

Patients And Methods: A cohort of 35 patients presenting with irCRS-like symptoms was studied, including 9 with irHLH-like manifestations and 8 with sepsis.

View Article and Find Full Text PDF

Radiotherapy-immunomodulated nanoplatform triggers both hypoxic and normoxic tumor associated antigens generation for robust abscopal effect and sustained immune memory.

Biomaterials

December 2024

Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Radiotherapy (RT) induced abscopal effect has garnered substantial attention, nevertheless, it is rarely observed in clinics, due to the tumor hypoxia-related radioresistance, inadequate immune stimulation, and immunosuppressive tumor microenvironment. Herein, we construct a radiotherapy-immunomodulated nanoplatform (THUNDER), which synergizes with RT and greatly triggers the generation of both hypoxic and normoxic tumor cells-derived tumor-associated antigens (TAAs), resulting in robust abscopal effect and sustained immune memory. THUNDER exhibits prolonged blood circulation and high tumor retention capacity.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!