UNC93B1 and Nucleic Acid-sensing Toll-like Receptors Mediate Host Resistance to Infection with Leishmania major

Schamber-Reis, Bruno Luiz Fonseca; Petritus, Patricia M.; Caetano, Bráulia Costa; Martinez, Espiridion R.; Okuda, Kendi; Golenbock, Douglas T.; Scott, Phillip; Gazzinelli, Ricardo T.

doi:10.1074/jbc.m112.407684

Cited by 38 publications

(37 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This shift could reflect changes in the cell types that principally mediate immune responses at different times in infection (discussed further below) or alternatively could be due to differential production or availability of TLR7 and TLR9 ligands by the parasite. Similar to our findings, other studies of bacterial and parasitic pathogens have found roles for multiple TLRs in sensing infection (66)(67)(68)(69). However, a seldom-addressed aspect of innate sensing that is highlighted by our study is that individual sensors can contribute to immune activation to various degrees during different stages of infection.…”

Section: Discussionsupporting

confidence: 78%

Toll-Like Receptor 7 Mediates Early Innate Immune Responses to Malaria

et al. 2013

View full text Add to dashboard Cite

Innate immune recognition of malaria parasites is the critical first step in the development of the host response. At present, Tolllike receptor 9 (TLR9) is thought to play a central role in sensing malaria infection. However, we and others have observed that Tlr9 ؊/؊ mice, in contrast to mice deficient in the downstream adaptor, Myeloid differentiation primary response gene 88 (MYD88), exhibit few deficiencies in immune function during early infection with the malaria parasite Plasmodium chabaudi, implying that another MYD88-dependent receptor also contributes to the antimalarial response. Here we use candidate-based screening to identify TLR7 as a key sensor of early P. chabaudi infection. We show that TLR7 mediates a rapid systemic response to infection through induction of cytokines such as type I interferons (IFN-I), interleukin 12, and gamma interferon. TLR7 is also required for induction of IFN-I by other species and strains of Plasmodium, including an etiological agent of human disease, P. falciparum, suggesting that malaria parasites harbor a common pathogen-associated molecular pattern (PAMP) recognized by TLR7. In contrast to the nonredundant requirement for TLR7 in early immune activation, sensing through both TLR7 and TLR9 was required for proinflammatory cytokine production and immune cell activation during the peak of parasitemia. Our findings indicate that TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses.

show abstract

Section: Discussionsupporting

confidence: 78%

Toll-Like Receptor 7 Mediates Early Innate Immune Responses to Malaria

et al. 2013

View full text Add to dashboard Cite

show abstract

“…There are several studies that support a role for TLR-9 in sensing L. major infection [106, 112–114]. TLR-9 deficiency in mice results in an enhanced T H 2 response, and only transiently inhibits the development of a T H 1 response and parasite clearance, as these mice are eventually able to heal their cutaneous lesions after L. major and L. brasiliensis infection [106, 112, 113, 115, 116]. Also, similar to TLR-9 −/− mice TLR-7 −/− mice are slightly more susceptible to L. major infection, but TLR-3 −/− mice are resistant to infection [115].…”

Section: Tlr Activation In Leishmania Infectionmentioning

confidence: 99%

“…TLR-9 deficiency in mice results in an enhanced T H 2 response, and only transiently inhibits the development of a T H 1 response and parasite clearance, as these mice are eventually able to heal their cutaneous lesions after L. major and L. brasiliensis infection [106, 112, 113, 115, 116]. Also, similar to TLR-9 −/− mice TLR-7 −/− mice are slightly more susceptible to L. major infection, but TLR-3 −/− mice are resistant to infection [115]. Infection of TLR-7/9 and TLR-3/7/9 knockout mice with L. major indicated that these mice were more susceptible to infection then single-gene deficient mice.…”

Section: Tlr Activation In Leishmania Infectionmentioning

confidence: 99%

Do You See What I See: Recognition of Protozoan Parasites by Toll-Like Receptors

Ghosh¹,

Stumhofer²

2014

CIR

View full text Add to dashboard Cite

Toll-like receptors (TLRs) are important for recognizing a variety of pathogens, including protozoan parasites, and initiating innate immune responses against them. TLRs are localized on the cell surface as well as in the endosome, and are implicated in innate sensing of these parasites. In this review, we will discuss recent findings on the identification of parasite-derived pathogen associated molecular patterns and the TLRs that bind them. The role of these TLRs in initiating the immune response against protozoan parasitic infections in vivo will be presented in the context of murine models of infection utilizing TLR-deficient mice. Additionally, we will explore evidence that TLRs and genetic variants of TLRs may impact the outcome of these parasitic infections in humans.

show abstract

“…Apart from its specificity for DNA, TLR9 has been shown to directly recognize hemozoin, an insoluble crystalline byproduct generated by Plasmodium falciparum during the process of detoxification after host hemoglobin is digested (Coban et al 2010). Additionally, TLR3, TLR7, TLR9, and UNC93B1 render host resistance to Leishmania major infection (Schamber-Reis et al 2013).…”

Section: Cd11bmentioning

confidence: 99%