Table 1.
Experimental studies indicating the role of IL-27 in Leishmaniasis disease.
| Parasite species | Mouse strain | Infective dose* | Infection site | Observation | References |
|---|---|---|---|---|---|
| L. major | WT C57BL/6 | 1 × 103 MP | Ear dermis | • P28 expression is increased in infected tissue at week two post-infection. • EBI3 expression becomes detectable in infected tissue at week five post-infection. |
(68) |
| L. major | WSX-1−/− C57BL/6 | 1 × 103 MP | Ear dermis | • The mice exhibit more severe lesions that were associated with the appearance of the IL-17+ CD4+ cells. • IL-27 administration prevents the development of abnormal Th17 cells during Leishmaniasis. • The mice display a low percentage of IL-10+ IFN-γ− CD4+ cells and more severe lesions at week 6 post-infection. |
(68) |
| L. major | WT C57BL/6 | 2 × 105 MP | Ear dermis | • CD11c+ DCs express P28 and EBI3 in draining lymph nodes at 24 h post-infection. | (69) |
| L. major | EBI3−/−C57BL/6 | 2 × 105 MP | Ear dermis | • Mice display greater susceptibility to infections with maximum parasites loads and lesion sizes at week six post-infection. • At weeks 2 and 4 post-infection, the IFN-γ secretion is lower, while the IL-4, IL-10, and IL-13 secretion were higher by L. major lysate-stimulated lymphocytes. • At early time points after infection, the Th1/Th2 balance is diverted toward Th2 cells. • Protective immunologic memory is not impaired in EBI3−/− mice. • IL-27 is essential for early control of parasite replication. |
(69) |
| L. major | WSX-1−/− C57BL/6 | 2 × 106 MP | Hind footpad | • Lymph node cells produce low Leishmania-induced IFN-γ levels at the initiation of infection. • Lymph node cells produce normal IFN-γ levels later in infection. • Mice produce considerable levels of IL-4 at the initial of infection. • Susceptibility to L. major is limited to the initial stages of infection. • The IP administration of anti-IL-4 antibody (every 4 days for the first 4 weeks of after infection) improves the IFN-γ production and host resistance. • The treatment with blocking anti-IL-4 antibody increases the number of IL-17+ CD4+ cells. |
(71) |
| L. major | WT BALB/c | 2 × 105 PM | †S.C into the hind footpad | • Administration of IL-27 reduces the parasite load. • Administration of IL-27 increases the survival rate. • Lymph node cells from IL-27-treated mice secrete higher IFN-γ quantities and lower IL-4 levels. |
(34) |
| L. donovani | WT C57BL/6 | 3 × 107 AM | Intravenously | • Splenic CD11chiMHCIIhi cDCs collected at days 21 and 28 post-infection express high IL-27 levels. • The DC-derived IL-27 may enhance the IFN-γ+ IL-10+ CD4+ cell polarization in vivo. |
(94) |
| L. donovani | WT BALB/c | 2 × 107−8 AM | Intravenously | • Infection promotes the IL-27 expression by splenic CD8α+ and CD4+ DC at days 1, 14, and 28 post-infection. | (90) |
| L. donovani | WSX-1−/− C57BL/6 | 1 × 107 AM | Intravenously | • Mice contain fewer parasites in livers on days 15, 30, and 60 after infection. • Mice show high resistance to L. donovani infection. • Mice display higher serum IFN-γ and TNF-α level on day 15 post-infection. • Mice display higher serum IL-12 levels on day 30 post-infection. • By day 60, levels of IL-12, TNF-α, and IFN-γ drop in mice. • The Leishmania antigen-stimulated spleen cells produce more amounts of IFN-γ and IL-12 on day 30 post-infection and produce more significant levels of NO on days 15 and 30 after infection. • Mice mount a robust Th1 cell response after L. donovani infection. • Mice display severe liver pathology. • The depletion of CD4+ T cells reduces liver pathology. • Neutralization of both TNF-α and IFN-γ reduces liver pathology. |
(92) |
| L. donovani | WT BALB/c | 2.5 × 107 AM | Intravenously | • Administration of the neutralizing anti-EBI3 antibody (and not anti-p28 antibody) to pathogen-infected mice reduces the parasite load in the spleen and liver and increase the TNF-α- and IFN-γ-secreting cells. | (101) |
| L. infantum | WT C57BL/6 WT BALB/c | 1 × 108 PM | Intravenously | • Serum IL-27 levels are increased early (at 4 days after infection) in the BALB/c mice, but not in C57BL/6 mice. •l The splenic DCs from BALB/c mice but not from C57BL/6 mice upregulate the expression of IL-27p28 24 h after infection. • IL-27 secretion by BMDCs from BALB/c was higher compared to C57BL/6, whereas the LPS-stimulated BMDCs from C57BL/6 mice produce more elevated amounts of IL-27 than BALB/c mice. • The administration of rIL-27 to in C57BL/6 increase the production of IL-10, while decrease IFN-γ and IL-12p70, and prevent the infiltration of neutrophils in the spleen at 24 h after treatment in comparison with infected non-treated animals. • Neutralization of IL-27 in acutely infected BALB/c decreases parasite burdens transiently reduces IL-10 and a transient increase in splenic IFN-γ producing CD4+ and CD8+ T cells. |
(102) |
| L. infantum | WT C57BL/6 | 1 × 107 PM | Intravenously | • High levels of the P28 subunit of IL-27 are detected in the spleen and liver at weeks 4 and 6 post-infection. • The expression of both IL-27R subunits, including WSX-1 and gp130, are upregulated at week 4 after infection. |
(103) |
| L. infantum | EBI3−/− C57BL/6 | 1 × 107 PM | Intravenously | • The parasite loads in the liver and spleen were lower at weeks 4 and 6 post-infection. • Mice produce higher IL-17A levels in both spleen and liver. • Restimulation splenocyte with L. infantum lysate leads to more IL-17A production. • Higher CXCL1expression was observed in the spleen, which causes a peak in neutrophil migration at week 4 post-infection in the spleen and liver. • When IL-17 was blocked, the mice become as susceptible as the C57BL/6 control. |
(103) |
| L. amazonensis | WT C57BL/6 | 5 × 105 PM | Hind footpad | • The IL-27 administration into the infected footpads (on days 2, 4, and 6 after infection) enhances the lesion sizes and parasite number in the footpads and the draining lymph nodes in weeks 2 and 3 following infection. | (116) |
*
AM, Amastigotes; MP, Metacyclic promastigotes; PM, Promastigotes;
†
SC, Subcutaneous.