Chemokines in host–parasiteinteractions in leishmaniasis

Teixeira, Maria Jânia; Teixeira, Clarissa; Andrade, Bruno B.; Barral‐Netto, Manoel; Barral, Aldina

doi:10.1016/j.pt.2005.11.010

Cited by 110 publications

(92 citation statements)

References 61 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The critical role of chemokines and their receptors in the development of immunity against a wide variety of pathogens has become a focus of interest in recent years [9,42]. Chemokines are often differentially induced in response to various stimuli or pathogens as a reflection of their varied ability to activate T cells and macrophages, influence T cell differentiation and recruit appropriate effector cells to the site of inflammation.…”

Section: Zoonotic Visceral Leishmaniasis (Zvl) Is Caused By Parasitesmentioning

confidence: 99%

Splenic immune responses during canine visceral leishmaniasis

Strauss-Ayali

Baneth

Jaffe³

2007

Vet. Res.

View full text Add to dashboard Cite

-Dogs are the main reservoir host for zoonotic visceral leishmaniasis caused by Leishmania infantum. In this study we investigated the immune response in spleens of L. infantum-infected dogs by measuring the mRNA expression levels for a wide panel of cytokines, transcription factors and chemokines. mRNA levels and parasite load were followed during 7 months of experimental infection and 14 months post-treatment, and were compared to naturally-infected (NI) dogs. Similarly, serum anti-Leishmania IgG and IgG subclass levels were measured during experimental infection. An increase in IFN-γ, T-bet, IP-10 and RANTES was found in the experimentally and NI dogs, implicating a substantial type-1 immune response during canine visceral leishmaniasis. IL-4, a type-2 associated cytokine, increased as early as one month after experimental infection, while IL-5 was high at later stages. Interestingly, the expression levels of the Treg-associated cytokines, IL-10 and TGF-β, did not change during the infection. Total anti-Leishmania IgG and IgG subclasses increased during the experimental infection. However, no association with specific cytokine patterns was observed. Parasite load in the spleens increased as early as one month postinfection and remained high until treatment. The load was higher in the polysymptomatic NI dogs than in the experimentally-infected dogs. This study indicates that both type-1 and type-2 immune responses occur in the spleen during canine L. infantum infection, and suggests that the early elevation of IL-4 might have a role in the persistence of parasites in the presence of high IFN-γ expression.canine visceral leishmaniasis / IFN-γ / IL-4 / T-bet / IP-10

show abstract

Section: Zoonotic Visceral Leishmaniasis (Zvl) Is Caused By Parasitesmentioning

confidence: 99%

Splenic immune responses during canine visceral leishmaniasis

Strauss-Ayali

Baneth

Jaffe³

2007

Vet. Res.

View full text Add to dashboard Cite

show abstract

“…These latter cytokines along with others have also been associated with macrophage deactivation (12,13). For example, inhibition of macrophage production of the antimicrobial gas NO has been associated with IL-10 and TGF-b (14), both of which are produced by leishmania-infected macrophages (15). IL-10 in particular has been identified as a critical factor that promotes disease expression after L. donovani infection, including the finding of unrestrained parasite replication in IL-10 transgenic mice (16).…”

mentioning

confidence: 99%

Myeloid Cell IL-10 Production in Response to Leishmania Involves Inactivation of Glycogen Synthase Kinase-3β Downstream of Phosphatidylinositol-3 Kinase

Nandan

Oliveira

Moeenrezakhanlou

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Leishmania disease expression has been linked to IL-10. In this study, we investigated the regulation of IL-10 production by macrophages infected with Leishmania donovani. Infection of either murine or human macrophages brought about selective phosphorylation of Akt-2 in a PI3K-dependent manner. These events were linked to phosphorylation and inactivation of glycogen synthase kinase-3β (GSK-3β) at serine 9, as the latter was abrogated by inhibition of either PI3K or Akt. One of the transcription factors that is negatively regulated by GSK-3β is CREB, which itself positively regulates IL-10 expression. Infection of macrophages with leishmania induced phosphorylation of CREB at serine 133, and this was associated with enhanced CREB DNA binding activity and induction of IL-10. Similar to phosphorylation of GSK-3β, both phosphorylation of CREB at serine 133 and CREB DNA binding activity were abrogated in cells treated with inhibitors of either PI3K or Akt prior to infection. Furthermore, disruption of this pathway either by inhibition of Akt or by overexpression of GSK-3β markedly attenuated IL-10 production in response to leishmania. Thus, GSK-3β negatively regulates myeloid cell IL-10 production in response to leishmania. Switching off GSK-3β promotes disease pathogenesis.

show abstract

“…In leishmaniasis, chemokine production represents one of the earliest detected responses to infection in vitro and in vivo (43). This includes production of CCL2, CCL3, and CXCL10 among others.…”

Section: Discussionmentioning

confidence: 99%