Toll-like receptor 2 recognition of the microsporidia Encephalitozoon spp. induces nuclear translocation of NF-κB and subsequent inflammatory responses

Jeffrey L Fischer, Colby Suire, Hollie Hale-Donze

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Microsporidia are obligate intracellular parasites that are ubiquitous in nature and have been recognized as causing an important emerging disease among immunocompromised individuals. Limited knowledge exists about the immune response against these organisms, and virtually nothing is known about the receptors involved in host recognition. Toll-like receptors (TLR) are pattern recognition receptors that bind to specific molecules found on pathogens and signal a variety of inflammatory responses. In this study, we show that both Encephalitozoon cuniculi and Encephalitozoon intestinalis are preferentially recognized by TLR2 and not by TLR4 in primary human macrophages. This is the first demonstration of host receptor recognition of any microsporidian species. TLR2 ligation is known to activate NF-κB, resulting in inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8). We found that the infection of primary human macrophages leads to the nuclear translocation of NF-κB in as early as 1 h and the subsequent production of TNF-α and IL-8. To verify the direct role of TLR2 parasite recognition in the production of these cytokines, the receptor was knocked down in primary human macrophages using small interfering RNA. This knockdown resulted in decreases in both the nuclear translocation of NF-κB and the levels of TNF-α and IL-8 after challenge with spores. Taken together, these experiments directly link the initial inflammatory response induced by Encephalitozoon spp. to TLR2 stimulation in human macrophages.

Original languageEnglish (US)
Pages (from-to)4737-4744
Number of pages8
JournalInfection and Immunity
Volume76
Issue number10
DOIs
StatePublished - Oct 1 2008

Fingerprint

Encephalitozoon
Microsporidia
Toll-Like Receptor 2
Macrophages
Interleukin-8
Tumor Necrosis Factor-alpha
Parasites
Encephalitozoon cuniculi
Pattern Recognition Receptors
Cytokine Receptors
Toll-Like Receptors
Spores
Small Interfering RNA
Ligation
Cytokines
Infection

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Toll-like receptor 2 recognition of the microsporidia Encephalitozoon spp. induces nuclear translocation of NF-κB and subsequent inflammatory responses. / Fischer, Jeffrey L; Suire, Colby; Hale-Donze, Hollie.

In: Infection and Immunity, Vol. 76, No. 10, 01.10.2008, p. 4737-4744.

Research output: Contribution to journalArticle

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