<i>Wolbachia</i>- and<i>Onchocerca volvulus</i>-Induced Keratitis (River Blindness) Is Dependent on Myeloid Differentiation Factor 88

Gillette‐Ferguson, Illona; Hise, Amy G.; Sun, Yan; Diaconu, Eugenia; McGarry, Helen F.; Taylor, Mark J.; Pearlman, Eric

doi:10.1128/iai.74.4.2442-2445.2006

Cited by 32 publications

(47 citation statements)

References 23 publications

(24 reference statements)

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“…Turner et al (68) have recently shown that immune tolerance induced by Wolbachia containing Brugia extracts to a range of TLR ligands is dependent on TLR2 and MyD88 but not TLR4. In our recent study of O. volvulus induced neutrophil recruitment in the cornea, Wolbachia-induced production of proinflammatory and chemotactic cytokines, development of corneal haze, and neutrophil activation were completely abrogated in MyD88 Ϫ/Ϫ mice (27), consistent with the data presented in this study. In summary, results from the current study extend our previous observations by demonstrating that the predominant innate receptors for Wolbachia and Wolbachia containing filaria are TLR2/TLR6 and not TLR4, and that signaling is entirely MyD88/Mal dependent.…”

Section: Discussionsupporting

confidence: 91%

“…Preparations contained Ͻ0.25 ng/ml endotoxin detectable by Limulus amoebocyte lysate assay (BioWhittaker). O. volvulus adult worms were recovered from s.c. nodules of infected individuals in Southwestern Côte d'Ivoire as previously described (27). Adult worms of A. viteae were obtained from TRS Laboratories and processed as described.…”

Section: Soluble Filarial Extractsmentioning

confidence: 99%

“…The corneal stroma of control and TLR gene knockout mice were injected with 4 g of soluble O. volvulus extract as previously described (27). After 24 h, eyes were removed, snap frozen in liquid nitrogen, and 5-m sections were incubated for 2 h with anti-macrophage Ab F4/80 diluted 1/100 in 1% FCS/PBS as described (9).…”

Section: Murine Model Of Keratitismentioning

confidence: 99%

“…Quantitative assessment of macrophage recruitment to the cornea in response to stromal injection of Wolbachia containing O. volvulus extract was performed in immunologically naive animals using our previously published protocol (27). As shown in Fig.…”

Section: Macrophage Recruitment To the Cornea In Response To O Volvumentioning

confidence: 99%

“…First, filarial-induced innate immune cellular activation is ablated if the parasites or infected animal hosts are pretreated with tetracycline antibiotics that partially eliminate intracellular Wolbachia (10,25,26). Second, Wolbachia isolated from filaria or from insect cell lines elicit inflammatory responses similar to those of filarial extracts containing Wolbachia (26,27). Third, in studies using a murine model of ocular onchocerciasis in which O. volvulus extract (containing Wolbachia) is injected into the corneal stroma, it was observed that the neutrophil infiltration and loss of corneal clarity that normally ensues was markedly reduced when Wolbachia-free Acanthocheilonema viteae or Wolbachia-depleted O. volvulus extracts were used (26,28).…”

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confidence: 99%

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Innate Immune Responses to Endosymbiotic Wolbachia Bacteria in Brugia malayi and Onchocerca volvulus Are Dependent on TLR2, TLR6, MyD88, and Mal, but Not TLR4, TRIF, or TRAM

Hise

Daehnel

Gillette‐Ferguson

et al. 2007

The Journal of Immunology

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106

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The discovery that endosymbiotic Wolbachia bacteria play an important role in the pathophysiology of diseases caused by filarial nematodes, including lymphatic filariasis and onchocerciasis (river blindness) has transformed our approach to these disabling diseases. Because these parasites infect hundreds of millions of individuals worldwide, understanding host factors involved in the pathogenesis of filarial-induced diseases is paramount. However, the role of early innate responses to filarial and Wolbachia ligands in the development of filarial diseases has not been fully elucidated. To determine the role of TLRs, we used cell lines transfected with human TLRs and macrophages from TLR and adaptor molecule-deficient mice and evaluated macrophage recruitment in vivo. Extracts of Brugia malayi and Onchocerca volvulus, which contain Wolbachia, directly stimulated human embryonic kidney cells expressing TLR2, but not TLR3 or TLR4. Wolbachia containing filarial extracts stimulated cytokine production in macrophages from C57BL/6 and TLR4−/− mice, but not from TLR2−/− or TLR6−/− mice. Similarly, macrophages from mice deficient in adaptor molecules Toll/IL-1R domain-containing adaptor-inducing IFN-β and Toll/IL-1R domain-containing adaptor-inducing IFN-β-related adaptor molecule produced equivalent cytokines as wild-type cells, whereas responses were absent in macrophages from MyD88−/− and Toll/IL-1R domain-containing adaptor protein (TIRAP)/MyD88 adaptor-like (Mal) deficient mice. Isolated Wolbachia bacteria demonstrated similar TLR and adaptor molecule requirements. In vivo, macrophage migration to the cornea in response to filarial extracts containing Wolbachia was dependent on TLR2 but not TLR4. These results establish that the innate inflammatory pathways activated by endosymbiotic Wolbachia in B. malayi and O. volvulus filaria are dependent on TLR2-TLR6 interactions and are mediated by adaptor molecules MyD88 and TIRAP/Mal.

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Section: Discussionsupporting

confidence: 91%

Section: Soluble Filarial Extractsmentioning

confidence: 99%

Section: Murine Model Of Keratitismentioning

confidence: 99%

Section: Macrophage Recruitment To the Cornea In Response To O Volvumentioning

confidence: 99%

mentioning

confidence: 99%

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Innate Immune Responses to Endosymbiotic Wolbachia Bacteria in Brugia malayi and Onchocerca volvulus Are Dependent on TLR2, TLR6, MyD88, and Mal, but Not TLR4, TRIF, or TRAM

Hise

Daehnel

Gillette‐Ferguson

et al. 2007

The Journal of Immunology

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106

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Toll-Like Receptors in CNS Parasitic Infections

Mishra

Gundra

Teale

2009

Current Topics in Microbiology and Immunology

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Parasite infections in the central nervous system (CNS) are a major cause of morbidity and mortality worldwide, second only to HIV infection. Finding appropriate therapeutic measures to control CNS parasite infections requires an understanding of the tissue-specific host response. CNS parasitic diseases are invariably associated with persistent T-helper 1 (Th1) cytokine-dependent proinflammatory responses. Although type 1 cytokine-dependent proinflammatory responses are essential to control several types of parasite infections, their persistent production contributes to the development of neuropathology with severe consequences. A family of proteins called Toll-like receptors (TLRs) plays a pivotal role in the induction of inflammatory cytokines during infections and tissue injury. Accumulating evidence indicates that in several CNS parasitic infections such as toxoplasmosis and sleeping sickness, host responses mediated through TLRs contribute to parasite clearance and host survival. However, TLR-mediated responses can also contribute to disease severity, as exemplified in cerebral malaria, neurocysticercosis and river blindness. Thus, TLRs influence the immunopathogenesis of CNS parasitic infections by mechanisms that can either benefit the host or further contribute to CNS pathology. This chapter discusses the immunopathogenesis of parasitic infections in the CNS and the role of TLRs in this process.

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