Modulation of Dendritic Cell Function by <i>Leishmania</i> Parasites

Soong, Lynn

doi:10.4049/jimmunol.180.7.4355

Cited by 96 publications

(92 citation statements)

References 70 publications

(70 reference statements)

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“…1). This finding was consistent with previous reports in human monocytes (12) and studies of murine DCs and M⌽s (32,43), indicating an impaired host innate immune response to L. amazonensis infection (24,35).…”

Section: Discussionsupporting

confidence: 83%

CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection

Vargas-Inchaustegui¹,

Hogg²,

Tulliano

et al. 2010

Infect Immun

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Leishmania (subgenus Viannia) braziliensis is the causative agent of mucocutaneous leishmaniasis (ML) in South America, and ML is characterized by excessive T-and B-cell responses to the parasite. We speculate that the unbalanced production of inflammatory mediators in response to L. braziliensis infection contributes to cell recruitment and disease severity. To test this hypothesis, we first examined the response of peripheral blood mononuclear cells (PBMCs) from healthy volunteers to L. braziliensis infection. We observed that while L. braziliensis infection induced the production of chemokine (C-X-C motif) ligand 10 (CXCL10) and interleukin-10 (IL-10) in human PBMCs and macrophages (M⌽s), enhanced expression of CXCL10 and its receptor, chemokine CXC receptor (CXCR3), was predominantly detected in CD14 ؉ monocytes. The chemoattractant factors secreted by L. braziliensis-infected cells were highly efficient in recruiting uninfected PBMCs (predominantly CD14؉ cells) through Transwell membranes. Serum samples from American tegumentary leishmaniasis (ATL) patients (especially the ML cases) had significantly higher levels of CXCL10, CCL4, and soluble tumor necrosis factor (TNF) receptor II (sTNFRII) than did those of control subjects. Our results suggest that, following L. braziliensis infection, the production of multiple inflammatory mediators by the host may contribute to disease severity by increasing cellular recruitment.

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Section: Discussionsupporting

confidence: 83%

CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection

Vargas-Inchaustegui¹,

Hogg²,

Tulliano

et al. 2010

Infect Immun

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“…(reviewed in [33]). The interaction of Leishmania promastigotes with DCs is generally accepted to cause activation of these cells [24,25], as shown by the enhanced expression of MHCII and co-stimulatory molecules (CD40, CD80, CD83 and CD86) and the ability to stimulate CD4 + T-cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A_2B adenosine receptor activation

et al. 2012

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Dendritic cells (DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs.While extracellular ATP exhibits proinflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. Bone marrowderived dendritic cells (BMDCs) from C57BL/6J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased major histocompatibility complex (MHC) class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A 2B adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A 2B receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response. Keywords: Adenosine receptors r CD40 r Dendritic cell r Ectonucleotidases r Leishmania amazonensis IntroductionLeishmaniasis is a group of diseases that are caused by obligate intracellular parasites of the genus Leishmania. Leishmania infections can result in a wide spectrum of clinical manifestations and disease outcome is determined both by the parasite species and by Correspondence: Dr. Luís C. C. Afonso e-mail: afonso@nupeb.ufop.br the host immune response. Leishmania amazonensis differs from other species because it is able to cause chronic non-healing lesions in mouse strains genuinely resistant to other Leishmania species, such as Leishmania braziliensis and Leishmania major [1][2][3]. In humans, L. amazonensis causes diffuse cutaneous leishmaniasis, a condition characterised by a lack of antigen-specific T-cell responses against the parasite [4].DCs play a critical role in orchestrating the innate and adaptive components of the immune system [5,6]. Immature DCs capture and process antigens located throughout the body. After contacting microorganisms or other inflammatory substances, C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu1204 Amanda B. Figueiredo et al. Eur. J. Immunol. 2012. 42: 1203-1215 these cells initiate their maturation process. DC maturation is characterised by increased expression of major histocompatibility complex (MHC) class II (MHCII) and co-stimulatory molecules, such as CD40, CD80, CD86 and CD54; decreased phagocytic capacity; increased cytokine secretion and expression of different chemokine receptors [5,7]. Extracellular ATP, which is accumulated following cellular injury, has important inf...

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“…Leishmania species induce a broad spectrum of pathologies in humans, ranging from cutaneous lesions to progressive fatal visceral disease (43). Although the determinants of pathogenesis remain unclear, the host immune response and the infecting Leishmania species contribute to the diverse clinical manifestations (57).…”

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confidence: 99%

Toll-Like Receptors Participate in Macrophage Activation and Intracellular Control of Leishmania (Viannia) panamensis

et al. 2011

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Toll-like receptors (TLRs) play a central role in macrophage activation and control of parasitic infections. Their contribution to the outcome of Leishmania infection is just beginning to be deciphered. We examined the interaction of Leishmania panamensis with TLRs in the activation of host macrophages. L. panamensis infection resulted in upregulation of TLR1, TLR2, TLR3, and TLR4 expression and induced tumor necrosis factor alpha (TNF-␣) secretion by human primary macrophages at comparable levels and kinetics to those of specific TLR ligands. The TLR dependence of the host cell response was substantiated by the absence of TNF-␣ production in MyD88/TRIF ؊/؊ murine bone marrow-derived macrophages and mouse macrophage cell lines in response to promastigotes and amastigotes. Systematic screening of TLR-deficient macrophages revealed that TNF-␣ production was completely abrogated in TLR4 ؊/؊ macrophages, consistent with the increased intracellular parasite survival at early time points of infection. TNF-␣ secretion was significantly reduced in macrophages lacking endosomal TLRs but was unaltered by a lack of TLR2 or MD-2. Together, these findings support the participation of TLR4 and endosomal TLRs in the activation of host macrophages by L. panamensis and in the early control of infection.

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Modulation of Dendritic Cell Function by Leishmania Parasites

Cited by 96 publications

References 70 publications

CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection

CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection

Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A_2B adenosine receptor activation

Toll-Like Receptors Participate in Macrophage Activation and Intracellular Control of Leishmania (Viannia) panamensis

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Modulation of Dendritic Cell Function by Leishmania Parasites

Cited by 96 publications

References 70 publications

CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection

CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection

Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation

Toll-Like Receptors Participate in Macrophage Activation and Intracellular Control of Leishmania (Viannia) panamensis

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Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A_2B adenosine receptor activation