The Dendritic Cell Receptor DC-SIGN Discriminates among Species and Life Cycle Forms of <i>Leishmania</i>

Colmenares, Marı́a; Corbí, Ángel L.; Turco, Salvatore J.; Rivas, Liliana A.

doi:10.4049/jimmunol.172.2.1186

Cited by 68 publications

(58 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Dedicated receptors for microbe Ags have been characterized on macrophages and DC. TLRs and DC-specific ICAM-grabbing nonintegrin have been shown to play crucial roles in modulating the innate responses to microorganisms (40,41) and to discriminate among Leishmania species (42). To date, very few data have indicated a direct recognition by lymphocytes of parasite Ags through these specific receptors, except for the recently reported reactivity of Leishmania lipophosphoglycan with TLR2 expressed on NK cells (43).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of the Natural Reactivity of Lymphocytes from Noninfected Individuals to Membrane-AssociatedLeishmania infantumAntigens

Sassi

Larguèche-Darwaz

Collette

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Membrane-associated Leishmania Ags (MLA) or soluble Leishmania Ags were used in vitro to stimulate cord blood or PBMC from healthy donors noninfected by Leishmania parasites. MLA, but not soluble Leishmania Ags, constantly induce strong proliferation of cord blood mononuclear cells and PBMC from noninfected individuals. Responding cells are CD3+, CD4+, TCRαβ+, CD45RO+, and CD45RA+ and secrete IFN-γ and IL-10, but not IL-4. MLA do not activate NK cells nor NKT cells. Membrane Ags also induce purified macrophages from noninfected individuals to secrete IL-10 and TNF-α, but have no effect on IL-1α or IL-12 secretion. The effects of MLA are proteinase K-sensitive and resistant to lipid extraction. The lymphoproliferative responses are inhibited by anti-HLA-DR Abs and require Ag processing by APCs, excluding that the biological effect of MLA could be attributed to a superantigen. Finally, TCR repertoire analysis shows that the T cell expansion induced by MLA uses TCR with various variable β segment rearrangements and CDR3 lengths, features much more characteristic to those observed with a polyclonal activator than with a conventional Ag. These results suggest a particular mechanism developed during the host’s natural response to Leishmania parasites that allows direct activation of naive CD4 lymphocytes by parasite membrane-associated Ags.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanisms of the Natural Reactivity of Lymphocytes from Noninfected Individuals to Membrane-AssociatedLeishmania infantumAntigens

Sassi

Larguèche-Darwaz

Collette

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…are a recurrent theme and are known to be further modulated by life cycle stage [33] and parasite species [34]. For example, the receptor DC-SIGN on human DC recognizes L. infantum and L. pifanoi but not L. major [34].…”

Section: Discussionmentioning

confidence: 99%

A critical role for lipophosphoglycan in proinflammatory responses of dendritic cells to Leishmania mexicana

et al. 2005

View full text Add to dashboard Cite

Recognition of pathogen-associated molecular patterns (PAMP) influences the response of dendritic cells (DC) and therefore development of innate and adaptive immunity. Different forms of Leishmania mexicana have distinct effects on DC, with promastigotes and amastigotes being activating and apparently neutral, respectively. We investigated whether stage-specific differences in surface composition might account for these distinct effects. Amastigotes and promastigotes lacking the lpg1 gene needed for lipophosphoglycan (LPG) biosynthesis could not activate DC in vitro. Genome-wide transcriptional profiling of DC infected with wild-type or mutant promastigotes or wildtype amastigotes revealed that wild-type promastigotes induce an inflammatory signature that is lacking in DC exposed to the other parasite forms. The proinflammatory response pattern was partly recovered by reconstitution of lpg1 expression in lpg1 -/-parasites, and exposure to purified LPG increased the expression of MHC class II and CD86 on DC. Infection with wild-type but not lpg1 -/-promastigotes increased the number of activated DC in draining lymph nodes, and this was correlated with lower early parasite burdens in wild-type-infected animals. These in vivo and in vitro results suggest an LPG-dependent activation of DC that contributes to host defense and agree with the notion that the parasites evolved under immune pressure to downregulate PAMP expression in mammalian hosts.

show abstract

“…Colmenares et al (2002) identified the C-type lectin, ICAM-3-grabbing nonintegrin (DC-SIGN) as the putative receptor on dendritic cells for L. pifanoi and L. infantum amastigotes. These molecules are parasite species-restricted since another C-type lectin; L-SIGN was shown to be a receptor for L. infantum and not L. pifanoi (Colmenares et al, 2004). Internalization of particles by these C-type lectins does not result in activation of dendritic cells.…”

Section: Parasite Entry Mechanismsmentioning

confidence: 99%

The amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection and persist

Kima

2007

International Journal for Parasitology

139

View full text Add to dashboard Cite

Leishmania are dimorphic protozoan parasites that live as flagellated forms in the gut of their sandfly vector and as aflagellated forms in their mammalian hosts. Although both parasite forms can infect macrophages and dendritic cells, they elicit distinct responses from mammalian cells. Amastigotes are the parasites forms that persist in the infected host; they infect cells recruited to lesions and disseminate the infection to secondary sites. In this review I discuss studies that have investigated the mechanisms that Leishmania amastigotes employ to harness the host cell's response to infection. It should be acknowledged that our understanding of the mechanisms deployed by Leishmania amastigotes to modulate the host cell's response to infection is still rudimentary. Nonetheless, the results show that amastigote interactions with mammalian cells promote the production of antiinflammatory cytokines such as IL-10 and TGF-ß while suppressing the production of IL-12, superoxide and nitric oxide. An underlying issue that is considered is how these parasites that reside in sequestered vacuolar compartments target host cell processes in the cytosol or the nucleus; does this occur through the release of parasite molecules from parasitophorous vacuoles or by engaging and sustaining signaling pathways throughout the course of infection?

show abstract

The Dendritic Cell Receptor DC-SIGN Discriminates among Species and Life Cycle Forms of Leishmania

Cited by 68 publications

References 40 publications

Mechanisms of the Natural Reactivity of Lymphocytes from Noninfected Individuals to Membrane-AssociatedLeishmania infantumAntigens

Mechanisms of the Natural Reactivity of Lymphocytes from Noninfected Individuals to Membrane-AssociatedLeishmania infantumAntigens

A critical role for lipophosphoglycan in proinflammatory responses of dendritic cells to Leishmania mexicana

The amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection and persist

Contact Info

Product

Resources

About