Cytokine and transcription factor profiles in the skin of dogs naturally infected by Leishmania (Leishmania) chagasi presenting distinct cutaneous parasite density and clinical status

Abstract

The immune response in the skin of dogs infected with Leishmania chagasi and its association with distinct levels of tissue parasitism and clinical progression of canine visceral leishmaniasis (CVL) are poorly understood and limited studies are available. A detailed analysis of the profiles of cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-13, TGF-β1 and TNF-α) and transcription factors (T-bet, GATA-3 and FOXP3) in the skin of 35 naturally infected dogs was carried out using real-time PCR alongside determinations of skin parasite density and the clinical status of CVL. A mixed cytokine profile with high levels of expression of IFN-γ, TNF-α and IL-13 was determined in asymptomatic dogs. Additionally, the levels of transcription factors GATA-3 and FOXP3 were correlated with the asymptomatic disease. A mixed cytokine profile was also observed during active CVL. Moreover, high levels of IL-10 and TGF-β1, concomitant with the low expression of IL-12, may represent a key condition that allows persistence of parasite replication in the skin. The results obtained indicate that in asymptomatic disease or lower levels of skin parasite density, a mixed inflammatory, regulatory immune response profile may be of major relevance for both the maintenance of the clinical status of the dogs as well as for parasite persistence and replication at low levels.

Animal Models for the Study of Leishmaniasis Immunology

“…Moreover, the levels of transcription factors GATA-3 and FOXP3 were correlated with the asymptomatic disease. These results indicate that in addition to the mixed cytokine profile, the enhanced expression of their associated transcription factors plays an important role in the clinical status of Leishmania infected dogs 69 . The role of Th2 type cytokines in canine VL has not yet been defined.…”

Pathologic Mechanisms Underlying the Clinical Findings in Canine Leishmaniosis due to Leishmaniainfantum/chagasi

“…136 Interestingly, amastigote density has been positively linked to specific areas of the skin (eg, ear pinnae), local cytokine (eg, IL-10, TGF-1) and chemokine milieu (eg, CCD, CC14), and circulating immune cells. 64,90,91 Within the inflammatory infiltrate, the predominating macrophages can be epithelial, vacuolated, or apoptotic. 11,148 Typical cutaneous microscopic lesions are consistent with orthokeratotic or parakeratotic hyperkeratosis, acanthosis, crusting, and ulceration in the epidermis and with inflammation of the dermis and occasionally panniculus, appearing in various histologic patterns (eg, interstitial, lichenoid, nodal, diffuse, periadnexal).…”

Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum

“…Moreover, these dogs were the most permissive to replication of parasites, likely as an aftermath of the suppressive effect of IL-10 and TGF-␤ on phagocytes (56). Similarly, the increase of parasite load in lymph node, skin, spleen, and intestine associated with the Treg response has been demonstrated in dogs infected by L. infantum (17,18,57,58). These results emphasize the important role of Treg in parasite spreading and point to a pivotal chromosomal region for susceptibility to L. infantum.…”

“…The adaptive response to canine Leishmania infection is markedly mixed, since L. infantum induces Th1 and T regulatory (Treg) responses. Treg lymphocytes inhibit activity of effector phagocytes and prevent exacerbation of inflammation; however, they also allow the spreading of the parasite (17)(18)(19).…”