Distinct roles for MyD88 and toll-like receptor 2 during Leishmania braziliensis infection in mice

Diego A. Vargas-Inchaustegui, Wendy Tai, Lijun Xin, Alison E. Hogg, David B. Corry, Lynn Soong

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

We have previously reported that Leishmania braziliensis infection can activate murine dendritic cells (DCs) and upregulate signaling pathways that are essential for the initiation of innate immunity. However, it remains unclear whether Toll-like receptors (TLRs) are involved in L. braziliensis-mediated DC activation. To address this issue, we generated bone marrow-derived DCs from MyD88-/- and TLR2-/- mice and examined their responsiveness to parasite infection. While wild-type DCs were efficiently activated to produce cytokines and prime naïve CD4+ T cells, L. braziliensis-infected MyD88-/- DCs exhibited less activation and decreased production of interleukin-12 (IL-12) p40. Furthermore, MyD88 -/- mice were more susceptible to infection in that they developed larger and prolonged lesions compared to those in control mice. In sharp contrast, the lack of TLR2 resulted in an enhanced DC activation and increased IL-12 p40 production after infection. As such, L. braziliensis-infected TLR2-/- DCs were more competent in priming naïve CD4+ T cells in vitro than were their controls, findings which correlated with an increased gamma interferon production in vivo and enhanced resistance to infection. Our results suggest that while MyD88 is indispensable for the generation of protective immunity to L. braziliensis, TLR2 seems to have a regulatory role during infection.

Original languageEnglish (US)
Pages (from-to)2948-2956
Number of pages9
JournalInfection and Immunity
Volume77
Issue number7
DOIs
StatePublished - Jul 2009

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Leishmania braziliensis
Toll-Like Receptor 2
Dendritic Cells
Infection
Interleukin-12
T-Lymphocytes
Parasitic Diseases
Toll-Like Receptors
Innate Immunity
Interferon-gamma
Immunity
Up-Regulation
Bone Marrow
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Distinct roles for MyD88 and toll-like receptor 2 during Leishmania braziliensis infection in mice. / Vargas-Inchaustegui, Diego A.; Tai, Wendy; Xin, Lijun; Hogg, Alison E.; Corry, David B.; Soong, Lynn.

In: Infection and Immunity, Vol. 77, No. 7, 07.2009, p. 2948-2956.

Research output: Contribution to journalArticle

Vargas-Inchaustegui, Diego A. ; Tai, Wendy ; Xin, Lijun ; Hogg, Alison E. ; Corry, David B. ; Soong, Lynn. / Distinct roles for MyD88 and toll-like receptor 2 during Leishmania braziliensis infection in mice. In: Infection and Immunity. 2009 ; Vol. 77, No. 7. pp. 2948-2956.
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