Mechanisms of Immunity to Ehrlichia mutis

A Model of Monocytotropic Ehrlichiosis

Hui Min Feng, David Walker

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Ehrlichia species can cause life-threatening infections or chronic persistent infections. Mechanisms of protective immunity were examined in an Ehrlichia muris mouse model of monocytotropic ehrlichiosis. C57BL/6 mice possessed strong genetic resistance to E. muris of an undetermined mechanism. CD8 T lymphocytes were particularly important, as revealed by 81% fatalities for E. muris-infected, major histocompatibility complex class I gene knockout mice compared with no deaths for wild-type C3H mice. Moreover, 80% of C3H mice depleted of CD8 and CD4 cells died of E. muris infection compared with only 44% of CD4 cell-depleted mice. CD8 T lymphocytes were demonstrated for the first time in an Ehrlichia infection to exhibit cytotoxic T-lymphocyte activity against Ehrlichia-infected target cells. Both gamma interferon and tumor necrosis factor were shown to play synergistic roles in protective immunity in vivo for the first time, as demonstrated by 75% fatalities when both cytokines were neutralized compared with minimal mortality when they were depleted separately. Passive transfer of antibodies, but not Fab fragments, to E. muris protected C3H/SCID mice against lethal infection. The mechanism of increased susceptibility (22% lethality) of C57BL/6 major histocompatibility complex class II gene knockout mice and CD4 cell-depleted C3H mice (i.e., through a gamma interferon or antibody mechanism), as well as the more important role of CD8 T lymphocytes (in the form of cytotoxic T-lymphocyte activity and/or gamma interferon production), remains to be elucidated. Protective immunity against monocytotropic E. muris is mediated by a combination of CD8 and CD4 T lymphocytes, gamma interferon, tumor necrosis factor alpha, and antibodies.

Original languageEnglish (US)
Pages (from-to)966-971
Number of pages6
JournalInfection and Immunity
Volume72
Issue number2
DOIs
StatePublished - Feb 2004

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Ehrlichia
Ehrlichiosis
Inbred C3H Mouse
Immunity
Interferon-gamma
T-Lymphocytes
Infection
Gene Knockout Techniques
Cytotoxic T-Lymphocytes
Major Histocompatibility Complex
Knockout Mice
Tumor Necrosis Factor-alpha
MHC Class I Genes
MHC Class II Genes
Immunoglobulin Fab Fragments
Passive Immunization
SCID Mice
Antibodies
Inbred C57BL Mouse
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Mechanisms of Immunity to Ehrlichia mutis : A Model of Monocytotropic Ehrlichiosis. / Feng, Hui Min; Walker, David.

In: Infection and Immunity, Vol. 72, No. 2, 02.2004, p. 966-971.

Research output: Contribution to journalArticle

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