keyword
https://read.qxmd.com/read/32733814/nk-cells-negatively-regulate-cd8-t-cells-to-promote-immune-exhaustion-and-chronic-toxoplasma-gondii-infection
#1
Daria L Ivanova, Ryan Krempels, Stephen L Denton, Kevin D Fettel, Giandor M Saltz, David Rach, Rida Fatima, Tiffany Mundhenke, Joshua Materi, Ildiko R Dunay, Jason P Gigley
NK cells regulate CD4+ and CD8+ T cells in acute viral infection, vaccination, and the tumor microenvironment. NK cells also become exhausted in chronic activation settings. The mechanisms causing these ILC responses and their impact on adaptive immunity are unclear. CD8+ T cell exhaustion develops during chronic Toxoplasma gondii ( T. gondii ) infection resulting in parasite reactivation and death. How chronic T. gondii infection impacts the NK cell compartment is not known. We demonstrate that NK cells do not exhibit hallmarks of exhaustion...
2020: Frontiers in Cellular and Infection Microbiology
https://read.qxmd.com/read/31604804/the-il-12-and-il-23-dependent-nk-cell-response-is-essential-for-protective-immunity-against-secondary-toxoplasma-gondii-infection
#2
Daria L Ivanova, Tiffany M Mundhenke, Jason P Gigley
NK cells can develop cell-intrinsic memory-like characteristics. Whether they develop these characteristics during Toxoplasma gondii infection is unknown. We addressed this question and dissected the mechanisms involved in secondary NK cell responses using a vaccine-challenge mouse model of T. gondii infection. NK cells were required for control of and survival after secondary T. gondii infection. NK cells increased in number at the reinfection site and produced IFN-γ. To test if these T. gondii experienced NK cells were intrinsically different from naive NK cells, we performed NK cell adoptive transfer into RAG2/cγ-chain-/- mice, NK cell fate mapping, and RAG1-/- mice vaccine-challenge experiments...
October 11, 2019: Journal of Immunology
https://read.qxmd.com/read/30873151/innate-lymphoid-cells-in-protection-pathology-and-adaptive-immunity-during-apicomplexan-infection
#3
REVIEW
Daria L Ivanova, Stephen L Denton, Kevin D Fettel, Kerry S Sondgeroth, Juan Munoz Gutierrez, Berit Bangoura, Ildiko R Dunay, Jason P Gigley
Apicomplexans are a diverse and complex group of protozoan pathogens including Toxoplasma gondii, Plasmodium spp., Cryptosporidium spp., Eimeria spp., and Babesia spp. They infect a wide variety of hosts and are a major health threat to humans and other animals. Innate immunity provides early control and also regulates the development of adaptive immune responses important for controlling these pathogens. Innate immune responses also contribute to immunopathology associated with these infections. Natural killer (NK) cells have been for a long time known to be potent first line effector cells in helping control protozoan infection...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30079054/microbiome-composition-in-both-wild-type-and-disease-model-mice-is-heavily-influenced-by-mouse-facility
#4
Kristopher D Parker, Shannon E Albeke, Jason P Gigley, Allan M Goldstein, Naomi L Ward
Murine models have become essential tools for understanding the complex interactions between gut microbes, their hosts, and disease. While many intra-facility factors are known to influence the structure of mouse microbiomes, the contribution of inter-facility variation to mouse microbiome composition, especially in the context of disease, remains under-investigated. We replicated microbiome experiments using identical mouse lines housed in two separate animal facilities and report drastic differences in composition of microbiomes based upon animal facility of origin...
2018: Frontiers in Microbiology
https://read.qxmd.com/read/28174736/paths-to-gi-research-in-the-wild-west-tales-from-wyoming
#5
EDITORIAL
Kristopher D Parker, Jason P Gigley, Naomi L Ward
No abstract text is available yet for this article.
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://read.qxmd.com/read/27721814/comparative-analysis-of-conventional-natural-killer-cell-responses-to-acute-infection-with-toxoplasma-gondii-strains-of-different-virulence
#6
Daria L Ivanova, Rida Fatima, Jason P Gigley
Conventional natural killer (cNK) cells, members of group 1 innate lymphoid cells, are a diverse cell subpopulation based on surface receptor expression, maturation, and functional potential. cNK cells are critical for early immunity to Toxoplasma gondii via IFNγ production. Acute cNK cell responses to infection with different strains of T. gondii have not yet been characterized in detail. Here, we comprehensively performed this analysis with Type I virulent RH, Type II avirulent ME49, and fully attenuated Type I cps1-1 strains...
2016: Frontiers in Immunology
https://read.qxmd.com/read/27611938/huntingtons-disease-mice-infected-with-toxoplasma-gondii-demonstrate-early-kynurenine-pathway-activation-altered-cd8-t-cell-responses-and-premature-mortality
#7
David W Donley, Andrew R Olson, Merl F Raisbeck, Jonathan H Fox, Jason P Gigley
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent life-long infection in immune-competent individuals...
2016: PloS One
https://read.qxmd.com/read/26915066/the-diverse-role-of-nk-cells-in-immunity-to-toxoplasma-gondii-infection
#8
Jason P Gigley
No abstract text is available yet for this article.
February 2016: PLoS Pathogens
https://read.qxmd.com/read/25197644/nk-cells-in-mucosal-defense-against-infection
#9
REVIEW
Daria Ivanova, Ryan Krempels, Jennyfer Ryfe, Kaitlyn Weitzman, David Stephenson, Jason P Gigley
Conventional natural killer cells (NK cells) provide continual surveillance for cancer and rapid responses to infection. They develop in the bone marrow, emerge as either NK precursor cells, immature, or mature cells, and disperse throughout the body. In the periphery NK cells provide critical defense against pathogens and cancer and are noted to develop features of adaptive immune responses. In the tightly regulated and dynamic mucosal tissues, they set up residency via unknown mechanisms and from sources that are yet to be defined...
2014: BioMed Research International
https://read.qxmd.com/read/22832368/t-cell-exhaustion-in-protozoan-disease
#10
REVIEW
Jason P Gigley, Rajarshi Bhadra, Magali M Moretto, Imtiaz A Khan
Protozoan parasites cause severe morbidity and mortality in humans worldwide, especially in developing countries where access to chemotherapeutic agents is limited. Although parasites initially evoke a robust immune response, subsequent immunity fails to clear infection, ultimately leading to the chronic stage. This enigmatic situation was initially addressed in chronic viral models, where T cells lose their function, a phenomenon referred to as 'exhaustion'. However, recent studies demonstrate that this paradigm can be extended to protozoan diseases as well, although with notable differences...
September 2012: Trends in Parasitology
https://read.qxmd.com/read/22539813/pd-1-mediated-attrition-of-polyfunctional-memory-cd8-t-cells-in-chronic-toxoplasma-infection
#11
Rajarshi Bhadra, Jason P Gigley, Imtiaz A Khan
We reported earlier that during chronic toxoplasmosis CD8(+) T cells become functionally exhausted with concomitant PD-1 upregulation, leading to eventual host mortality. However, how immune exhaustion specifically mediates attrition of CD8 polyfunctionality, a hallmark of potent T-cell response, during persistent infections has not been addressed. In this study, we demonstrate that PD-1 is preferentially expressed on polyfunctional memory CD8(+) T cells, which renders them susceptible to apoptosis. In vitro blockade of the PD-1-PD-L1 pathway dramatically reduces apoptosis of polyfunctional and interferon γ(+)/granzyme B(-) memory but not effector CD8(+) T cells...
July 1, 2012: Journal of Infectious Diseases
https://read.qxmd.com/read/21949017/cutting-edge-cd40-cd40-ligand-pathway-plays-a-critical-cd8-intrinsic-and-extrinsic-role-during-rescue-of-exhausted-cd8-t-cells
#12
Rajarshi Bhadra, Jason P Gigley, Imtiaz A Khan
CD8 exhaustion mediated by an inhibitory programmed death-1-programmed death ligand-1 (PD-L1) pathway occurs in several chronic infections, including toxoplasmosis. Although blockade of the programmed death-1-PD-L1 pathway revives this response, the role of costimulatory receptors involved in this rescue has not been ascertained in any model of CD8 exhaustion. This report demonstrates that one such costimulatory pathway, CD40-CD40L, plays a critical role during rescue of exhausted CD8 T cells. Blockade of this pathway abrogates the ameliorative effects of anti-PD-L1 treatment on CD8 T cells...
November 1, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/21695169/plasmacytoid-dc-from-aged-mice-down-regulate-cd8-t-cell-responses-by-inhibiting-cdc-maturation-after-encephalitozoon-cuniculi-infection
#13
Jason P Gigley, Imtiaz A Khan
Age associated impairment of immune function results in inefficient vaccination, tumor surveillance and increased severity of infections. Several alterations in adaptive immunity have been observed and recent studies report age related declines in innate immune responses to opportunistic pathogens including Encephalitozoon cuniculi. We previously demonstrated that conventional dendritic cells (cDC) from 9-month-old animals exhibit sub-optimal response to E. cuniculi infection, suggesting that age associated immune senescence begins earlier than expected...
2011: PloS One
https://read.qxmd.com/read/21687650/cd8-t-cells-and-toxoplasma-gondii-a-new-paradigm
#14
Jason P Gigley, Rajarshi Bhadra, Imtiaz A Khan
CD8 T cells are essential for control of Toxoplasma gondii infection. Once activated they undergo differentiation into short-lived effector and memory precursor effector cells. As effector cells, CD8 T cells exert immune pressure on the parasite via production of inflammatory cytokines and through their cytolytic activity. Once immune control has been established, the parasite encysts and develops into chronic infection regulated by the memory CD8 T-cell population. Several signals are needed for this process to be initiated and for development of fully differentiated memory CD8 T cells...
2011: Journal of Parasitology Research
https://read.qxmd.com/read/21668315/the-cd8-t-cell-road-to-immunotherapy-of-toxoplasmosis
#15
REVIEW
Rajarshi Bhadra, Jason P Gigley, Imtiaz A Khan
Toxoplasma gondii infection induces a robust CD8 T-cell immunity that is critical for keeping chronic infection under control. In studies using animal models, it has been demonstrated that the absence of this response can compromise the host ability to keep chronic infection under check. Therapeutic agents that facilitate the induction and maintenance of CD8 T-cell response against the pathogen need to be developed. In the last decade, major strides in understanding the development of effector and memory response, particularly in viral and tumor models, have been made...
June 2011: Immunotherapy
https://read.qxmd.com/read/21576466/control-of-toxoplasma-reactivation-by-rescue-of-dysfunctional-cd8-t-cell-response-via-pd-1-pdl-1-blockade
#16
Rajarshi Bhadra, Jason P Gigley, Louis M Weiss, Imtiaz A Khan
In this study, we document that Toxoplasma gondii differentiation and reactivation are mediated by systemic CD8 T-cell dysfunction during chronic infection. We demonstrate that CD8(+) T-cell exhaustion occurs despite control of parasitemia during early-chronic toxoplasmosis. During later phases, these cells become exhausted, leading to parasite reactivation and mortality. Concomitant with increased CD8(+) T-cell apoptosis and decreased effector response, this dysfunction is characterized by a graded elevation in expression of inhibitory receptor PD-1 on these cells in both lymphoid and nonlymphoid tissue...
May 31, 2011: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/21531875/type-ii-toxoplasma-gondii-ku80-knockout-strains-enable-functional-analysis-of-genes-required-for-cyst-development-and-latent-infection
#17
Barbara A Fox, Alejandra Falla, Leah M Rommereim, Tadakimi Tomita, Jason P Gigley, Corinne Mercier, Marie-France Cesbron-Delauw, Louis M Weiss, David J Bzik
Type II Toxoplasma gondii KU80 knockouts (Δku80) deficient in nonhomologous end joining were developed to delete the dominant pathway mediating random integration of targeting episomes. Gene targeting frequency in the type II Δku80 Δhxgprt strain measured at the orotate (OPRT) and the uracil (UPRT) phosphoribosyltransferase loci was highly efficient. To assess the potential of the type II Δku80 Δhxgprt strain to examine gene function affecting cyst biology and latent stages of infection, we targeted the deletion of four parasite antigen genes (GRA4, GRA6, ROP7, and tgd057) that encode characterized CD8(+) T cell epitopes that elicit corresponding antigen-specific CD8(+) T cell populations associated with control of infection...
September 2011: Eukaryotic Cell
https://read.qxmd.com/read/21057089/a-cell-impermeable-cyclosporine-a-derivative-reduces-pathology-in-a-mouse-model-of-allergic-lung-inflammation
#18
Molly A Balsley, Miroslav Malesevic, Erik J Stemmy, Jason Gigley, Rosalyn A Jurjus, Dallen Herzog, Michael I Bukrinsky, Gunter Fischer, Stephanie L Constant
Although the main regulators of leukocyte trafficking are chemokines, another family of chemotactic agents is cyclophilins. Intracellular cyclophilins function as peptidyl-prolyl cis-trans isomerases and are targets of the immunosuppressive drug cyclosporine A (CsA). Cyclophilins can also be secreted in response to stress factors, with elevated levels of extracellular cyclophilins detected in several inflammatory diseases. Extracellular cyclophilins are known to have potent chemotactic properties, suggesting that they might contribute to inflammatory responses by recruiting leukocytes into tissues...
December 15, 2010: Journal of Immunology
https://read.qxmd.com/read/19797073/long-term-immunity-to-lethal-acute-or-chronic-type-ii-toxoplasma-gondii-infection-is-effectively-induced-in-genetically-susceptible-c57bl-6-mice-by-immunization-with-an-attenuated-type-i-vaccine-strain
#19
Jason P Gigley, Barbara A Fox, David J Bzik
C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection...
December 2009: Infection and Immunity
https://read.qxmd.com/read/19218423/efficient-gene-replacements-in-toxoplasma-gondii-strains-deficient-for-nonhomologous-end-joining
#20
Barbara A Fox, Jessica G Ristuccia, Jason P Gigley, David J Bzik
A high frequency of nonhomologous recombination has hampered gene targeting approaches in the model apicomplexan parasite Toxoplasma gondii. To address whether the nonhomologous end-joining (NHEJ) DNA repair pathway could be disrupted in this obligate intracellular parasite, putative KU proteins were identified and a predicted KU80 gene was deleted. The efficiency of gene targeting via double-crossover homologous recombination at several genetic loci was found to be greater than 97% of the total transformants in KU80 knockouts...
April 2009: Eukaryotic Cell
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