Pentoxifylline down modulate in vitro T cell responses and attenuate pathology in Leishmania and HTLV-I infections

Jesus, Amélia Ribeiro de; Luna, Tania; Almeida, Roque Pacheco de; Machado, Paulo Roberto Lima; Carvalho, Edgar M.

doi:10.1016/j.intimp.2008.03.020

Cited by 19 publications

(13 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this, in a study on visceral leishmaniasis, high TNF-α concentrations were related to disease progression (Kaye et al 2004). Additionally, TNF-α inhibition healed ulcers in patients with American cutaneous leishmaniasis (Ribeiro de Jesus et al 2008). In accordance with these studies, our results also suggest that TNF-α is involved not in protection, but in tissue damage and pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the expression of toll-like receptors 2 and 4 and cytokine production during experimental Leishmania chagasi infection

Cezário¹,

Oliveira²,

Peresi³

et al. 2011

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Analysis of the expression of toll-like receptors 2 and 4 and cytokine production during experimental Leishmania chagasi infection

Cezário¹,

Oliveira²,

Peresi³

et al. 2011

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

“…There is evidence that an exacerbated Th1 immune response with high production of IFN-γ and TNF-α, as well a lack of regulatory response, is associated with lesion development in CL and mucosal leishmaniasis, as reviewed by Ribeiro-de-Jesus et al (2008). On the other hand, these cytokines are fundamental to parasite killing (Liew et al 1990).…”

Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni antigens alter the cytokine response in vitro during cutaneous leishmaniasis

Bafica

Cardoso

Oliveira

et al. 2011

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

“…However, excessive inflammation is known to play an important role in human pathology and infection with Leishmania (Viannia) organisms (10–12). An exaggerated immune response (high production of Th1 cytokines with reduced levels of IL-10) is associated with enhanced disease severity in infected patients (13–15). Additionally, there is a correlation with lesion size and the frequency of antigen specific cytokine producing cells (16); further, reductions in IFN-γ and TNF-α are found following disease resolution (17).…”

Section: Introductionmentioning

confidence: 99%

The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection

Ehrlich

Castilho

Goldsmith-Pestana

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Leishmania (Viannia) parasites are etiological agents of cutaneous leishmaniasis in the New World. Infection is characterized by a mixed Th1/Th2 inflammatory response, which contributes to disease pathology. However, the role of T regulatory cells (Treg) in Leishmania (Viannia) disease pathogenesis is unclear. Using the mouse model of chronic L. (V.) panamensis infection, we have examined the hypothesis that Treg functionality contributes to control of pathogenesis. Upon infection, T regulatory cells (CD4+Foxp3+) presented with a dysregulated phenotype, in that they produced IFN-γ, expressed Tbet and had a reduced ability to suppress T cell proliferation in vitro. Targeted ablation of Tregs resulted in enlarged lesions, increased parasite load and enhanced production of IL-17 and IFN-γ with no change in IL-10 and IL-13 levels. Thus, indicating that an increased inflammatory response was commensurate with disease exacerbation and that the remaining impaired Treg cells were important in regulation of disease pathology. Conversely, adoptive transfer of Tregs from naïve mice halted disease progression, lowered parasite burden and reduced cytokine production (IL-10, IL-13, IL-17, IFN-γ). As Tregs appeared important for controlling infection, we hypothesized the expansion of Tregs could be used as an immunotherapeutic treatment approach. As a proof of principle, chronically infected mice were treated with rIL-2-anti-IL-2 antibody complex to expand Tregs. Treatment transitorily increased numbers and percentage of Treg (draining lymph node, spleen), that resulted in reduced cytokine responses, ameliorated lesions and reduced parasite load (105-fold). Thus, immunotherapy targeting Tregs could provide an alternate treatment strategy for leishmaniasis caused by L. (Viannia) parasites.

show abstract

Pentoxifylline down modulate in vitro T cell responses and attenuate pathology in Leishmania and HTLV-I infections

Cited by 19 publications

References 92 publications

Analysis of the expression of toll-like receptors 2 and 4 and cytokine production during experimental Leishmania chagasi infection

Analysis of the expression of toll-like receptors 2 and 4 and cytokine production during experimental Leishmania chagasi infection

Schistosoma mansoni antigens alter the cytokine response in vitro during cutaneous leishmaniasis

The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection

Contact Info

Product

Resources

About