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Divanshu Shukla, Himanshu Singh Chandel, Sunit Srivastava, Prashant Chauhan, Surya Prakash Pandey, Ashok Patidar, Raja Banerjee, Debprasad Chattopadhyay, Bhaskar Saha
Toll-like receptors (TLRs) recognize the pathogen-associated molecular patterns (PAMPs) and induce host-protective immune response. The role of the profilin-recognizing TLR11/TLR12 in Leishmania infection is unknown. Herein, we report that TLR11/ TLR12 expression increases in virulent L. major-infected macrophages but is prevented by miltefosine, an anti-leishmanial drug. While lipohosphoglycan (LPG) increases, LPG or TLR2 blockade prevents, the heightened TLR11/TLR12 expression. LPG-TLR2 interaction triggers MyD88- and TIRAP-mediated signaling enhancing ERK-1/2 activation and increased production of IL-10 that promotes TLR11/TLR12 expression...
October 7, 2017: Cytokine
Delin Qi, Mingzhe Xia, Yan Chao, Yongli Zhao, Rongrong Wu
Hypoxia plays an important role in regulating a variety of physiological responses as well as in pathological situations, but to date the roles of Toll-like receptors (TLRs) in fish in response to hypoxia are still poorly understood. Here, we sequenced the transcriptome of G. eckloni and identified the members of TLR family by scanning transcriptome, and then investigated the expression profiles of a complete set of TLRs in G. eckloni in response to acute hypoxia (4 h at DO = 0.3 ± 0.1 mg/L). The de novo-assembled transcriptome consisted of a total of 162,235 transcripts, further clustered into 110,231 unigenes...
July 8, 2017: Fish & Shellfish Immunology
Urs B Müller, Jonathan C Howard
Nobody doubts that infections have imposed specialisations on the mammalian genome. However sufficient information is usually missing to attribute a specific genomic modification to pressure from a specific pathogen. Recent studies on mechanisms of mammalian resistance against the ubiquitous protozoan parasite, Toxoplasma gondii, have shown that the small rodents presumed to be largely responsible for transmission of the parasite to its definitive host, the domestic cat, possess distinctive recognition proteins, and interferon-inducible effector proteins (IRG proteins) that limit the potential virulence of the parasite...
August 2016: Current Opinion in Microbiology
Susweta Das Mitra, Bibek Ranjan Shome, Bhuvana Mani, D Velu, Apala Banerjee, Kiran Bankar, Sankar Kumar Ghosh, Sandip Santra, K P Suresh, Habibur Rahman
Streptococcus uberis causing mastitis is a growing challenge to the dairy industry. Molecular, epidemiological and population structure studies have revealed clonal diversity among the infecting strains. In this study, mouse intramammary infection model was used to uncover the host immune response to two epidemiologically important live strains of S. uberis (SU1and SU2) obtained from subclinical case of mastitis possessing specific and unique multi locus sequence types (ST), pulsed field gel electrophoresis (PFGE) pulsotypes and virulence profiles...
July 10, 2016: Gene
Kevin W Tosh, Lara Mittereder, Sandra Bonne-Annee, Sara Hieny, Thomas B Nutman, Steven M Singer, Alan Sher, Dragana Jankovic
As a major natural host for Toxoplasma gondii, the mouse is widely used for the study of the immune response to this medically important protozoan parasite. However, murine innate recognition of toxoplasma depends on the interaction of parasite profilin with TLR11 and TLR12, two receptors that are functionally absent in humans. This raises the question of how human cells detect and respond to T. gondii. In this study, we show that primary monocytes and dendritic cells from peripheral blood of healthy donors produce IL-12 and other proinflammatory cytokines when exposed to toxoplasma tachyzoites...
January 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Lori M Neal, Laura J Knoll
Ly6C+ inflammatory monocytes are essential to host defense against Toxoplasma gondii, Listeria monocytogenes and other infections. During T. gondii infection impaired inflammatory monocyte emigration results in severe inflammation and failure to control parasite replication. However, the T. gondii factors that elicit these monocytes are unknown. Early studies from the Remington laboratory showed that mice with a chronic T. gondii infection survive lethal co-infections with unrelated pathogens, including L. monocytogenes, but a mechanistic analysis was not performed...
June 2014: PLoS Pathogens
Jennifer Morger, Jaroslav Bajnok, Kellyanne Boyce, Philip S Craig, Michael T Rogan, Zhao-Rong Lun, Geoff Hide, Barbara Tschirren
Toxoplasma gondii is a highly successful parasite with a worldwide prevalence. Small rodents are the main intermediate hosts, and there is growing evidence that T. gondii modifies their behaviour. Chronically infected rodents show impaired learning capacity, enhanced activity, and, most importantly, a reduction of the innate fear towards cat odour. This modification of host behaviour ensures a successful transmission of T. gondii from rodents to felids, the definitive hosts of the parasite. Given the negative fitness consequences of this behavioural manipulation, as well as an increased mortality during the acute phase of infection, we expect rodents to evolve potent resistance mechanisms that prevent or control infection...
August 2014: Infection, Genetics and Evolution
Ricardo T Gazzinelli, Rondon Mendonça-Neto, Jingtao Lilue, Jonathan Howard, Alan Sher
Recent studies have revealed remarkable species specificity of the Toll-like receptors (TLRs) TLR11 and TLR12 and the immunity-related GTPase (IRG) proteins that are essential elements for detection and immune control of Toxoplasma gondii in mice, but not in humans. The biological and evolutionary implications of these findings for the T. gondii host-pathogen relationship and for human disease are discussed.
February 12, 2014: Cell Host & Microbe
Danilo Pietretti, Marleen Scheer, Inge R Fink, Nico Taverne, Huub F J Savelkoul, Herman P Spaink, Maria Forlenza, Geert F Wiegertjes
Like other vertebrate Toll-like receptors (TLRs), the TLRs of teleost fish can be subdivided into six major families, each of which recognize a general class of molecular patterns. However, there also are a number of Tlrs with unknown function, the presence of which seems unique to the bony fish, among which is Tlr20. We identified full-length complementary DNA (cDNA) sequences for tlr20 of zebrafish and common carp, two closely related fish species. Zebrafish have six copies of tlr20, whereas carp express only a single copy...
February 2014: Immunogenetics
Megan Raetz, Alexey Kibardin, Carolyn R Sturge, Reed Pifer, Haiying Li, Ezra Burstein, Keiko Ozato, Sergey Larin, Felix Yarovinsky
TLRs play a central role in the innate recognition of pathogens and the activation of dendritic cells (DCs). In this study, we establish that, in addition to TLR11, TLR12 recognizes the profilin protein of the protozoan parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to the parasite. Similar to TLR11, TLR12 is an endolysosomal innate immune receptor that colocalizes and interacts with UNC93B1. Biochemical experiments revealed that TLR11 and TLR12 directly bind to T. gondii profilin and are capable of forming a heterodimer complex...
November 1, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
Charles F Aylsworth, Yasser A Aldhamen, Sergey S Seregin, Sarah Godbehere, Andrea Amalfitano
The safe and effective activation of the innate and adaptive immune systems are crucial in the implementation of immunotherapeutic modalities for the prevention and treatment of human diseases. Eimeria antigen (EA) and its recombinantly expressed analog (rEA) are extremely effective activators of innate immunity in mice. The effects of rEA in the mouse are primarily mediated through the TLR11/12 MyD88 signaling system. Human cells lack functional TLR11 and TLR12, suggesting that rEA would not be effective in providing beneficial immune activation in humans...
August 2013: Human Immunology
Sylvie M A Quiniou, Pierre Boudinot, Eva Bengtén
A comprehensive survey of channel catfish Toll-like receptors (TLRs) was undertaken following a genomic PCR approach based on degenerate primers. Twenty different TLRs were identified in channel catfish. Channel catfish TLR sequences were characterized by phylogenetic analysis based on their conserved Toll/interleukin-1 receptor domain and by in-depth analysis of leucine-rich repeat (LRR) motifs of the ligand binding extracellular domain (ECD). The catfish have representatives of all the TLR types defined in vertebrates with the exception of TLR6, TLR10, TLR11, TLR12, TLR13, TLR15, TLR23, and TLR24...
July 2013: Immunogenetics
Bettina L Lee, Joanne E Moon, Jeffrey H Shu, Lin Yuan, Zachary R Newman, Randy Schekman, Gregory M Barton
UNC93B1, a multipass transmembrane protein required for TLR3, TLR7, TLR9, TLR11, TLR12, and TLR13 function, controls trafficking of TLRs from the endoplasmic reticulum (ER) to endolysosomes. The mechanisms by which UNC93B1 mediates these regulatory effects remain unclear. Here, we demonstrate that UNC93B1 enters the secretory pathway and directly controls the packaging of TLRs into COPII vesicles that bud from the ER. Unlike other COPII loading factors, UNC93B1 remains associated with the TLRs through post-Golgi sorting steps...
2013: ELife
Warrison A Andrade, Maria do Carmo Souza, Espiridion Ramos-Martinez, Kamalpreet Nagpal, Miriam S Dutra, Mariane B Melo, Daniella C Bartholomeu, Sankar Ghosh, Douglas T Golenbock, Ricardo T Gazzinelli
"Triple-defective" (3d) mice carrying a mutation in UNC93B1, a chaperone for the endosomal nucleic acid-sensing (NAS) Toll-like receptors TLR3, TLR7, and TLR9, are highly susceptible to Toxoplasma gondii infection. However, none of the single or even the triple NAS-TLR-deficient animals recapitulated the 3d susceptible phenotype to experimental toxoplasmosis. Investigating this further, we found that while parasite RNA and DNA activate innate immune responses via TLR7 and TLR9, TLR11 and TLR12 working as heterodimers are required for sensing and responding to Toxoplasma profilin...
January 16, 2013: Cell Host & Microbe
A Alicia Koblansky, Dragana Jankovic, Hyunju Oh, Sara Hieny, Waradon Sungnak, Ramkumar Mathur, Matthew S Hayden, Shizuo Akira, Alan Sher, Sankar Ghosh
Toll-like receptor 11 (TLR11) recognizes T. gondii profilin (TgPRF) and is required for interleukin-12 production and induction of immune responses that limit cyst burden in Toxoplasma gondii-infected mice. However, TLR11 only modestly affects survival of T. gondii-challenged mice. We report that TLR12, a previously uncharacterized TLR, also recognized TgPRF. TLR12 was sufficient for recognition of TgPRF by plasmacytoid dendritic cells (pDCs), whereas TLR11 and TLR12 were both required in macrophages and conventional DCs...
January 24, 2013: Immunity
Danica K Hickey, John V Fahey, Charles R Wira
This study investigates the cyclic changes in innate immunity in the female reproductive tract (FRT) of mice during the estrous cycle. By examining uterine and vaginal tissues and secretions we show that innate immunity varies with the stage of the estrous cycle and site in the FRT. Secretions from the uterine lumen contained cytokines and chemokines that were significantly higher at proestrus and estrus relative to that measured at diestrus. In contrast, analysis of vaginal secretions indicated that only IL-1β and CXCL1/mouse KC changed during the cycle, with highest levels measured at diestrus and estrus...
2013: Innate Immunity
Seung-Jin Kim, Youngshim Choi, Youn-Hee Choi, Taesun Park
Obesity is characterized by low-grade and chronic inflammation, a phenomenon explained with a new term, metaflammation. Recent studies suggest that adipocytes may play an important role in the physiological regulation of immune responses in fat deposits via toll-like receptor (TLR) signaling cascades. This study investigates the role of the visceral as well as subcutaneous adipose tissues in the development of metaflammation by characterizing the tissue-specific expression profiles of TLRs and downstream signaling molecules and explores the differential responsiveness of TLR-mediated proinflammatory signaling cascades to diet-induced obesity (DIO) and obesity induced by a leptin gene deficiency...
February 2012: Journal of Nutritional Biochemistry
Rachael S Hageman, Magalie S Leduc, Christina R Caputo, Shirng-Wern Tsaih, Gary A Churchill, Ron Korstanje
Identifying the genes underlying quantitative trait loci (QTL) for disease is difficult, mainly because of the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals, test candidate genes, and define pathways affected by these QTL. In this study, we mapped three significant QTL and one suggestive QTL for an increased albumin-to-creatinine ratio on chromosomes (Chrs) 1, 4, 15, and 17, respectively, in a cross between the inbred MRL/MpJ and SM/J strains of mice...
January 2011: Journal of the American Society of Nephrology: JASN
Tiandi Wei, Jing Gong, Shaila C Rössle, Ferdinand Jamitzky, Wolfgang M Heckl, Robert W Stark
So far, 13 groups of mammalian Toll-like receptors (TLRs) have been identified. Most TLRs have been shown to recognize pathogen-associated molecular patterns from a wide range of invading agents and initiate both innate and adaptive immune responses. The TLR ectodomains are composed of varying numbers and types of leucine-rich repeats (LRRs). As the crystal structures are currently missing for most TLR ligand-binding ectodomains, homology modeling enables first predictions of their three-dimensional structures on the basis of the determined crystal structures of TLR ectodomains...
January 2011: Journal of Molecular Modeling
Bibhuti B Mishra, Uma Mahesh Gundra, Judy M Teale
The functions of Toll-like receptors (TLRs) 11-13 in central nervous system (CNS) infections are currently unknown. Using a murine model of neurocysticercosis, we investigated the expression and distribution of TLRs 11-13 by using both gene specific real-time PCR analysis and in situ immunofluorescence microscopy in both control and neurocysticercosis brains. In the mock infected brain, mRNAs of TLRs 11-13 were constitutively expressed. Parasite infection caused an increase of both mRNAs and protein levels of all three TLRs by several fold...
December 12, 2008: Journal of Neuroinflammation
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