Tissue Cytokine Responses in Canine Visceral Leishmaniasis

Abstract

To elucidate the local tissue cytokine response of dogs infected with Leishmania chagasi, cytokine mRNA levels were measured in bone marrow aspirates from 27 naturally infected dogs from Brazil and were compared with those from 5 uninfected control animals. Interferon-gamma mRNA accumulation was enhanced in infected dogs and was positively correlated with humoral (IgG1) but not with lymphoproliferative responses to Leishmania antigen in infected dogs. Increased accumulation of mRNA for interleukin (IL)-4, IL-10, and IL-18 was not observed in infected dogs, and mRNA for these cytokines did not correlate with antibody or proliferative responses. However, infected dogs with detectable IL-4 mRNA had significantly more severe symptoms. IL-13 mRNA was not detectable in either control or infected dogs. These data suggest that clinical symptoms are not due to a deficiency in interferon-gamma production. However, in contrast to its role in human visceral leishmaniasis, IL-10 may not play a key immunosuppressive role in dogs.

Splenic immune responses during canine visceral leishmaniasis

“…Nevertheless, it was significantly elevated relatively early post-infection in the oligosymptomatic EI dogs studied here. Interestingly, even though IL-4 expression was not previously found to be significantly elevated in the bone marrow of L. infantum-infected dogs, higher expression was associated with the presence of more severe clinical signs [31]. Moreover, IL-4 expression in skin biopsies obtained from infected dogs was found to be significantly higher than in similar samples taken from uninfected dogs and was correlated with increased parasite load in skin lesions [7].…”

“…Earlier studies to determine if specific IgG subclass levels in L. infantum-infected dogs are associated with the clinical outcome and hence with resistance or susceptibility to the disease, produced conflicting results [6,14,24,38]. However, these studies used commercial polyclonal anti-sera to canine IgG1 and IgG2, while we used the same monoclonal antibody panel (IgG1, IgG2, IgG3 and IgG4) previously employed by Quinnell et al [31,32]. We found a general up-regulation of the total IgG, as well as of all IgG subclasses during experimental infection similarly to what was previously found for L. infantum NI dogs using this antibody panel, and also for HVL patients [11,32].…”

“…Expression of IL-4 mRNA was found in the bone marrow of some symptomatic dogs [31], and significantly higher IL-4 expression was recently detected locally in skin lesions from L. infantum-infected dogs [7]. Interferon-γ expression of antigen stimulated PBMC, in skin lesions and in the bone marrow of infected dogs was shown to be elevated [7,10,31,41].…”

“…Involvement of IL-10 in the immune response of Leishmania-infected dogs has not yet been established, since the expression of IL-10 mRNA in antigen stimulated PBMC or the bone marrow of infected dogs was not elevated during the course of an experimental infection, or in naturallyinfected dogs, respectively [31,36]. Expression of IL-4 mRNA was found in the bone marrow of some symptomatic dogs [31], and significantly higher IL-4 expression was recently detected locally in skin lesions from L. infantum-infected dogs [7]. Interferon-γ expression of antigen stimulated PBMC, in skin lesions and in the bone marrow of infected dogs was shown to be elevated [7,10,31,41].…”

“…All L. infantum EI dogs were classified as oligosymptomatic according to the semi-quantitative scoring method suggested by Quinnell et al [31]. These dogs (n = 6) demonstrated relatively mild skin involvement manifested as hair loss and fine exfoliation of the ear tips (pineal alopecia) (5/6).…”