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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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© 2016 Habib et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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: 16 Feb 2019 14:55


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