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NK cell-mediated regulation of protective memory responses against intracellular ehrlichial pathogens

Habib, S and El Andaloussi, A and Hisham, A and Ismail, N (2016) NK cell-mediated regulation of protective memory responses against intracellular ehrlichial pathogens. PLoS ONE, 11 (4).

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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-γ-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-γ 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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Habib, S
El Andaloussi, A
Hisham, A
Ismail, Nnai13@pitt.eduNAI13
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 April 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 11
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0153223
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Date Deposited: 31 Aug 2016 17:31
Last Modified: 22 Jun 2021 11:55


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