Cutaneous host defense in leishmaniasis: interaction of isolated dermal macrophages and epidermal Langerhans cells with the insect-stage promastigote

Locksley, Richard M.; Heinzel, Frederick P.; Fankhauser, J; Nelson, C S; Sadick, Michael D.

doi:10.1128/iai.56.2.336-342.1988

Cited by 41 publications

(19 citation statements)

References 36 publications

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“…Similar to murine pDC, infection was not detected in primary human pDC (10). In addition, LC did not ingest significant numbers of parasites, which is in contrast to some prior murine studies (11–13), but not others (14). Interestingly, primary myDC behaved very similar to murine skin DC in that they preferentially took up the amastigote life form in a comparably slow fashion (Fig.…”

Section: Resultscontrasting

confidence: 99%

Human primary dendritic cell subsets differ in their IL‐12 release in response to Leishmania major infection

Zahn

Kirschsiefen²,

Jonuleit

et al. 2010

Experimental Dermatology

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Immunity against leishmaniasis has primarily been studied in experimental infections of mice. It was shown that infected skin dendritic cells (DC) are critical for the induction of protection against this pathogen, and targeting skin DC in vaccination approaches in mice has proven to be successful. However, little is known about the contribution of human DC subsets from the skin to primary immunity against this pathogen. In this study, we have analysed the interaction between different human DC subsets and Leishmania major. Primary human myeloid and monocyte-derived DC ingested the parasite comparable to that of murine skin DC, and this resulted in DC activation and IL-12 release, a cytokine essential for the induction of Th1 ⁄ Tc1-dependent protection. Interestingly, both Langerhans cells and plasmacytoid DC did not appear to contribute to protection in humans. Thus, in leishmaniasis, both murine and human data suggest that dermal inflammatory DC appear to be superior in promoting protection.

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Section: Resultscontrasting

confidence: 99%

Human primary dendritic cell subsets differ in their IL‐12 release in response to Leishmania major infection

Zahn

Kirschsiefen²,

Jonuleit

et al. 2010

Experimental Dermatology

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“…The present study demonstrates that LC-like skin DC (FSDDC) that have been propagated from strains of mice that are susceptible (BALB/c) or resistant (C57BL/6) to L. major-induced cutaneous leishmaniasis are phenotypically and functionally equivalent. Like C57BL/6 cells, BALB/c FSDDC selectively internalized and responded to L. major amastigotes as compared to metacyclic promastigotes (see [17,21]). Infection of DC from both strains was accompanied by up-regulation of cell surface levels of MHC Ag and co-stimulatory molecules, and cytokine release.…”

Section: Discussionmentioning

confidence: 99%

Leishmania major-infected murine Langerhans cell-like dendritic cells from susceptible mice release IL-12 after infection and vaccinate against experimental cutaneous Leishmaniasis

et al. 2000

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Leishmania major‐infected C57BL / 6 skin‐dendritic cells (DC) are activated and release cytokines (including IL‐12 p70), and likely initiate protective Th1 immunity in vivo (von Stebut, E. et al., J. Exp. Med. 188: 1547 – 1552). To characterize differences in DC function in mice that are genetically susceptible (BALB / c) and resistant (C57BL / 6) to cutaneous leishmaniasis, we analyzed the effects of L. major on Langerhans cell‐like, fetal skin‐derived DC (FSDDC) from both strains. BALB / c‐ and C57BL / 6‐FSDDC ingested similar numbers of amastigotes, but did not ingest metacyclic promastigotes. Like C57BL / 6‐FSDDC, infection of BALB / c‐FSDDC led to up‐regulation of MHC class I and II antigens, CD40, CD54, and CD86 within 18 h. L. major‐induced BALB / c DC activation also led to the release of TNF‐α, IL‐6 and IL‐12 p40 into 18‐h supernatants. Infected BALB / c‐ and C57BL / 6‐DC both released small amounts of IL‐12 p70 within 72 h. Additional stimulation with IFN‐γ and / or anti‐CD40 induced the release of more IL‐12 p70 from infected BALB / c‐DC than C57BL / 6‐DC. Co‐culture of control or infected BALB / c‐ and C57BL / 6‐DC with naive syngeneic CD4+ T cells and soluble anti‐CD3 resulted in mixed, IFN‐γ‐predominant responses after restimulation with immobilized anti‐CD3. Finally, syngeneic L. major‐infected DC effectively vaccinated BALB / c mice against cutaneous leishmaniasis. Genetic susceptibility to L. major that results from induction of Th2 predominant immune responses after infection does not appear to reflect failure of skin DC to internalize or respond to parasites, or the inability of BALB / c T cells to mount a Th1 response to DC‐associated Leishmania antigens.

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“…LC, the DC of the epidermis, have been reported to be parasitized by L. major AM [22,24] but not PM [25]. DC are heterogeneous and in particular LC appear to differ from DC in the dermis and other tissues [26][27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Murine dendritic cells internalizeLeishmania major promastigotes, produce IL-12 p40 and stimulate primary T cell proliferationin vitro

et al. 1999

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Metacyclic Leishmania promastigotes (PM), transmitted by sand-fly bite, are likely to interact initially with cells of the dendritic cell (DC) lineage(s) in the epidermis or dermis. Epidermal Langerhans cells internalize L. major amastigotes (AM) and transport them to draining lymph nodes (Moll, H., Fuchs, H., Blank, C. and Röllinghoff, M., Eur. J. Immunol. 1993. 23: 1595) but little is known about the interaction of DC with PM. The present study demonstrates that DC are able to internalize PM and that the fate of the parasites within DC differs from that within macrophages (M ¤). DC took up small numbers of PM which did not differentiate into AM but appeared to be degraded; M ¤ internalized large numbers of PM into parasitophor-ous vacuoles where they differentiated into AM. In response to direct stimulation with PM, DC from both C3H ("resistant" to L. major infection) and BALB/c ("susceptible") up-regulated production of IL-12 p40. In contrast, IL-12 production by M ¤ was not detected. DC exposed to either metacyclic PM or PM culture supernatants were also able to stimulate proliferative responses in lymph node T cells from naive mice. These data indicate that DC have the capacity to promote protective Th1 immune responses in Leishmania infection and suggest that DC exposed to PM may be useful in immunotherapy and vaccination.

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Cutaneous host defense in leishmaniasis: interaction of isolated dermal macrophages and epidermal Langerhans cells with the insect-stage promastigote

Cited by 41 publications

References 36 publications

Human primary dendritic cell subsets differ in their IL‐12 release in response to Leishmania major infection

Human primary dendritic cell subsets differ in their IL‐12 release in response to Leishmania major infection

Leishmania major-infected murine Langerhans cell-like dendritic cells from susceptible mice release IL-12 after infection and vaccinate against experimental cutaneous Leishmaniasis

Murine dendritic cells internalizeLeishmania major promastigotes, produce IL-12 p40 and stimulate primary T cell proliferationin vitro

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