Novel Loci Controlling Parasite Load in Organs of Mice Infected With Leishmania major, Their Interactions and Sex Influence

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00509060" target="_blank" >RIV/68378050:_____/19:00509060 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/19:10399821

Result on the web

<a href="https://www.frontiersin.org/articles/10.3389/fimmu.2019.01083/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fimmu.2019.01083/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fimmu.2019.01083" target="_blank" >10.3389/fimmu.2019.01083</a>

Result language

angličtina

Original language name

Novel Loci Controlling Parasite Load in Organs of Mice Infected With Leishmania major, Their Interactions and Sex Influence

Original language description

Leishmaniasis is a serious health problem in many countries, and continues expanding to new geographic areas including Europe and USA. This disease, caused by parasites of Leishmania spp. and transmitted by phiebotomine sand flies, causes up to 1.3 million new cases each year and despite efforts toward its functional dissection and treatment it causes 20-50 thousands deaths annually. Dependence of susceptibility to leishmaniasis on sex and host's genes was observed in humans and in mouse models. Several laboratories defined in mice a number of Lmr (Leishmania major response) genetic loci that control functional and pathological components of the response to and outcome of L. major infection. However, the development of its most aggressive form, visceral leishmaniasis, which is lethal if untreated, is not yet understood. Visceral leishmaniasis is caused by infection and inflammation of internal organs. Therefore, we analyzed the genetics of parasite load, spread to internal organs, and ensuing visceral pathology. Using a new PCR-based method of quantification of parasites in tissues we describe a network-like set of interacting genetic loci that control parasite load in different organs. Quantification of Leishmania parasites in lymph nodes, spleen and liver from infected F-2 hybrids between BALB/c and recombinant congenic strains CcS-9 and CcS-16 allowed us to map two novel parasite load controlling Leishmania major response loci, Lmr24 and Lmr27. We also detected parasite-controlling role of the previously described loci Lmr4, Lmr11, Lmr13, Lmr14, Lmr15, and Lmr25, and describe 8 genetic interactions between them. Lmr14, Lmr15, Lmr25, and Lmr27 controlled parasite load in liver and lymph nodes. In addition, Leishmania burden in lymph nodes but not liver was influenced by Lmr4 and Lmr24. In spleen, parasite load was controlled by Lmr11 and Lmr13. We detected a strong effect of sex on some of these genes. We also mapped additional genes controlling splenomegaly and hepatomegaly. This resulted in a systematized insight into genetic control of spread and load of Leishmania parasites and visceral pathology in the mammalian organism.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10603 - Genetics and heredity (medical genetics to be 3)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Immunology

ISSN

1664-3224

e-ISSN

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Volume of the periodical

10

Issue of the periodical within the volume

June

Country of publishing house

CH - SWITZERLAND

Number of pages

17

Pages from-to

1083

UT code for WoS article

000470989800001

EID of the result in the Scopus database

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