{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Habib S"],"funding":["NIAID NIH HHS"],"pagination":["e0153223"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4836677"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(4)"],"pubmed_abstract":["Ehrlichiae are gram-negative obligate intracellular bacteria that cause potentially fatal human monocytic ehrlichiosis. We previously showed that natural killer (NK) cells play a critical role in host defense against Ehrlichia during primary infection. However, the contribution of NK cells to the memory response against Ehrlichia remains elusive. Primary infection of C57BL/6 mice with Ehrlichia muris provides long-term protection against a second challenge with the highly virulent Ixodes ovatus Ehrlichia (IOE), which ordinarily causes fatal disease in naïve mice. Here, we show that the depletion of NK cells in E. muris-primed mice abrogates the protective memory response against IOE. Approximately, 80% of NK cell-depleted E. muris-primed mice succumbed to lethal IOE infection on days 8-10 after IOE infection, similar to naïve mice infected with the same dose of IOE. The lack of a recall response in NK cell-depleted mice correlated with an increased bacterial burden, extensive liver injury, decreased frequency of Ehrlichia-specific IFN-?-producing memory CD4+ and CD8+ T-cells, and a low titer of Ehrlichia-specific antibodies. Intraperitoneal infection of mice with E. muris resulted in the production of IL-15, IL-12, and IFN-? as well as an expansion of activated NKG2D+ NK cells. The adoptive transfer of purified E. muris-primed hepatic and splenic NK cells into Rag2-/-Il2rg-/- recipient mice provided protective immunity against challenge with E. muris. Together, these data suggest that E. muris-induced memory-like NK cells, which contribute to the protective, recall response against Ehrlichia."],"journal":["PloS one"],"pubmed_title":["NK Cell-Mediated Regulation of Protective Memory Responses against Intracellular Ehrlichial Pathogens."],"pmcid":["PMC4836677"],"funding_grant_id":["1R56AI097679-01","R56 AI097679"],"pubmed_authors":["Hisham A","Ismail N","Habib S","El Andaloussi A"],"additional_accession":[]},"is_claimable":false,"name":"NK Cell-Mediated Regulation of Protective Memory Responses against Intracellular Ehrlichial Pathogens.","description":"Ehrlichiae are gram-negative obligate intracellular bacteria that cause potentially fatal human monocytic ehrlichiosis. We previously showed that natural killer (NK) cells play a critical role in host defense against Ehrlichia during primary infection. However, the contribution of NK cells to the memory response against Ehrlichia remains elusive. Primary infection of C57BL/6 mice with Ehrlichia muris provides long-term protection against a second challenge with the highly virulent Ixodes ovatus Ehrlichia (IOE), which ordinarily causes fatal disease in naïve mice. Here, we show that the depletion of NK cells in E. muris-primed mice abrogates the protective memory response against IOE. Approximately, 80% of NK cell-depleted E. muris-primed mice succumbed to lethal IOE infection on days 8-10 after IOE infection, similar to naïve mice infected with the same dose of IOE. The lack of a recall response in NK cell-depleted mice correlated with an increased bacterial burden, extensive liver injury, decreased frequency of Ehrlichia-specific IFN-?-producing memory CD4+ and CD8+ T-cells, and a low titer of Ehrlichia-specific antibodies. Intraperitoneal infection of mice with E. muris resulted in the production of IL-15, IL-12, and IFN-? as well as an expansion of activated NKG2D+ NK cells. The adoptive transfer of purified E. muris-primed hepatic and splenic NK cells into Rag2-/-Il2rg-/- recipient mice provided protective immunity against challenge with E. muris. Together, these data suggest that E. muris-induced memory-like NK cells, which contribute to the protective, recall response against Ehrlichia.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016","modification":"2021-03-05T09:24:19Z","creation":"2019-03-26T22:57:49Z"},"accession":"S-EPMC4836677","cross_references":{"pubmed":["27092553"],"doi":["10.1371/journal.pone.0153223"]}}