<i>Leishmania braziliensis</i> Infection Induces Dendritic Cell Activation, ISG15 Transcription, and the Generation of Protective Immune Responses

Vargas-Inchaustegui, Diego A.; Luo, Xin; Soong, Lynn

doi:10.4049/jimmunol.180.11.7537

Cited by 74 publications

(83 citation statements)

References 52 publications

(60 reference statements)

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“…However, DC-NK cell cocultures did not further enhance DC or NK cell activation. Nevertheless, comparative studies with two developmental stages of L. amazonensis and L. braziliensis parasites confirmed our previous findings (42) and suggested to us that the lack of infectionmediated DC and NK cell activation was unique to L. amazonensis amastigotes.…”

Section: Cd40supporting

confidence: 71%

“…Axenic L. amazonensis amastigotes (strain LV78; obtained from Kwang-Poo Chang, Department of Microbiology and Immunology, Chicago Medical School) were maintained routinely in complete Grace's medium at 33°C (15). L. braziliensis amastigotes (LC1418) were freshly transformed from low-passage-number promastigotes and cultured in complete Grace's medium at 33°C and 5% CO 2 (42). To prepare heat-killed parasites, we incubated amastigotes (8 ϫ 10 7 /ml in phosphate-buffered saline [PBS]) in a 60°C water bath for 15 min, as described previously (32).…”

Section: Methodsmentioning

confidence: 99%

“…braziliensis amastigotes were capable of activating DCs. Because the infection with L. amazonensis amastigotes failed to induce DC and NK cell activation, we wanted to confirm whether this impairment was parasite species specific and performed similar studies using L. braziliensis amastigotes from short-term cultures (42). As shown in Fig.…”

Section: Cd40mentioning

confidence: 99%

“…Using different species (L. amazonensis, L. braziliensis, and L. major) and developmental stages of parasites, as well as murine bone marrow-derived DCs (BM-DCs), we have recently demonstrated a species-dependent impairment in DC activation during infection with L. amazonensis promastigotes (42,46) and a general lack of DC activation during infection with L. amazonensis amastigotes (37,45). Given that DC activation can be enhanced by NK cells through cell contactdependent and -independent mechanisms (14), we investigated whether NK cells would enhance DC responsiveness to Leish-mania parasites.…”

mentioning

confidence: 99%

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Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Sanabria¹,

Vargas-Inchaustegui²,

Luo³

et al. 2008

Infect Immun

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The importance of the interaction between natural killer (NK) cells and dendritic cells (DCs) in the expansion of antiviral and antitumor immune responses is well-documented; however, limited information on DC-NK cell interaction during parasitic infections is available. Given that some Leishmania parasites are known to prevent or suppress DC activation, we developed a DC-NK cell coculture system to examine the role of NK cells in modulating the functions of Leishmania-infected DCs. We found that the addition of freshly isolated, resting NK cells significantly promoted the activation of DCs that were preinfected with Leishmania amazonensis promastigotes and that these activated DCs, in turn, stimulated NK cell activation mostly via cell contact-dependent mechanisms. Notably, L. amazonensis amastigote infection failed to activate DCs, and this lack of DC activation could be partially reversed by the addition of preactivated NK (ANK) cells but not resting NK cells. Moreover, the adoptive transfer of ANK cells into L. amazonensis-infected mice markedly increased DC and T-cell activation and reduced tissue parasite loads at 1 and 3 weeks postinfection. These results suggest differential roles of DC-NK cell cross talk at different stages of Leishmania infection and provide new insight into the interplay of components of the innate immune system during parasitic infection.

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Section: Cd40supporting

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Cd40mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Sanabria¹,

Vargas-Inchaustegui²,

Luo³

et al. 2008

Infect Immun

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“…Depending on their maturation state, DCs have the ability to polarize distinct T cell subsets, such as T helper cells, regulatory T cells and cytotoxic T cells, controlling the outcome of infections due to pathogenic microorganisms. Several studies have demonstrated that DCs can be infected by Leishmania parasites but with conflicting results regarding the regulatory role of DCs in parasite growth and host susceptibility (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Low CD40 Expression Levels inLeishmaniaInfantum-Infected Bone Marrow Dendritic Cells Evoke Regulatory Responses by Down-Regulating Interleukin-12 Production: Role of ERK1/2

2014

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Dendritic cells (DCs) playa pivotal role in promoting resistance to leishmaniasis, both by activating CD4+ T cells and endorsing their differentiation into Th 1 cells by producing interleukin (IL)-12. High level ofIL-12 production, a decisive component ofthe DC maturation, requires not only microbial stimuli but also strong CD40-CD40L interactions. Until now, the mechanisms by which Leishmania (L.) infantum parasites affect DC functional maturation and consequently T cell polarization are not fully understood.In the present study, we investigated the response that is elicited when L. infantum promastigoteinfected bone marrow-derived DCs (BM-DCs) to CD40 engagement and this way mimicking DC-T cells interactions at the early stages of infection. We found that L. infantum promastigotes-infected BM-DCs following CD40 engagement were capable of inducing significant amounts ofTNF-a and IL-IO, whereas IL-12 production remained unaffected compared to infected untreated cells. Interestingly, infected BM-DCs did not up-regulate CD40 surface expression. On the other hand, BM-DC stimulation with soluble Leishmania antigen (SLA) resulted not only in significant increase of co-stimulatory molecule expression but also IL-12 and IL-IO production. CD40 engagement on L. infantum-infected BM-DCs sustained ERK1I2 activation induced by the parasite alone. Inhibition of ERK1I2 activation with the use of PD98059 inhibitor prior to CD40 engagement on L. infantum-infected BM-DCs resulted in significant up-regulation ofp38 MAPK phosphorylation and IL-12 production, whereas it did not affect TNF-a and IL-IO production. These findings suggest that L. infantum has evolved specific strategies to avoid efficient DC-T cell interactions by suppressing CD40 expression and consequently leading CD40 signaling pathways to ERK1I2 activation.

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Murine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease

et al. 2010

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Leishmania (Viannia) organisms are the most prevalent etiologic agents of human cutaneous leishmaniasis in the Americas. Nevertheless, our knowledge of the immunological mechanisms exploited by L. (Viannia) organisms remains limited and the mechanisms underlying disease are not well understood. Here, we report the development of a BALB/c mouse model of L. (V.) panamensis infection that is able to reproduce chronic disease, with persistent infection and clinically evident lesions for over 1 year. The immune response of the mouse resembles that found for L. (V.) panamensis-infected patients with chronic and recurrent lesions, presenting a mixed Th1/Th2 response with the presence of TNF-α, IFN-γ, IL-10 and IL-13. Using immunodeficient mice, the critical role for IL-13 and/or IL-4Rα in determining susceptibility to chronic infection was evident. With the induction of healing in the immunodeficient mice, increases in IFN-γ and IL-17 were found, concomitant with parasite control and elimination. Specifically, increases in CD4+ (but not CD8+) T cells producing IFN-γ were observed. These results suggest that IL-13 represents an important target for disease control of L. (V.) panamensis infection. This murine model should be useful to further understand the pathology associated with chronic disease and to develop methods for the treatment and prevention of leishmaniasis caused by L. (Viannia) parasites.

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Leishmania braziliensis Infection Induces Dendritic Cell Activation, ISG15 Transcription, and the Generation of Protective Immune Responses

Cited by 74 publications

References 52 publications

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Low CD40 Expression Levels inLeishmaniaInfantum-Infected Bone Marrow Dendritic Cells Evoke Regulatory Responses by Down-Regulating Interleukin-12 Production: Role of ERK1/2

Murine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease

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