We characterized key leukocyte immunophenotypes in the liver and spleen of naturally infected dogs from an area in Venezuela endemic for leishmaniasis. Dogs were classified as symptomatic or asymptomatic after serologic and physical analysis. Symptomatic dogs showed a higher parasite burden in the liver and spleen than asymptomatic dogs. The livers of asymptomatic dogs showed an effective immunity with well-organized granulomas walling off parasites in an environment of central memory CD44(lo), CD45RO(hi), activated effector CD44(hi), and CD45RO(hi) T cells. These granulomas also had many major histocompatibility class II+ cells and CD11c+ dendritic cells, and cells expressing CD18 and CD44. In contrast, symptomatic livers showed a non-organized and non-effective infiltrate composed of T cells and heavily parasitized Kupffer cells and a diminished expression of activation molecules. In the spleen, the immune responses of symptomatic and asymptomatic dogs were very similar. The results showed a distinct immune response against Leishmania chagasi in target organs.

Accessory signals, which include adhesion molecules, MHC-II molecules and cytokines, are necessary to foster the interaction between memory T cells and epidermal cells, that is required to promote cutaneous inflammatory responses. American cutaneous leishmaniasis (ACL) is characterized by a spectrum of immunological manifestations, and is a prototype disease for the study of regulatory mechanisms involved in immune protection against protozoal infection. In the present study, we show that diffuse cutaneous leishmaniasis (DCL) epidermis contains keratinocytes that do not express ICAM-1 and HLA-DR molecules. Langerhans cells (LC) are within normal values or somewhat lower, and a very few cells expressing the HB15 molecule--a new described member of the Ig superfamily--are found in such lesions. Mucocutaneous leishmaniasis (MCL) epithelium shows an increased expression of ICAM-1 and HLA-DR molecules, few HB15+ cells, and an absence of epithelial LC. Localized cutaneous leishmaniasis (LCL) epidermis displays ICAM-1+ keratinocytes organized in patches, a uniform expression of HLA-DR, hyperplasia of LC, and numerous HB15+ cells. In all forms of the disease, infiltrating T cells express more LFA-1 beta than LFA-1 alpha, but LFA-1 beta+ T cells are more abundant in LCL granulomas. In contrast, there are more LFA-1 alpha+ T cells in DCL and MCL than in LCL granulomas. LCL lesions also show the highest numbers of HB15+ cells within the granuloma. These results indicate the importance of adhesion molecules in ACL lesions, and open new possibilities for therapeutic schemes oriented towards the control of cell migration.

No abstract

No abstract

Innate lymphoid cells (ILCs) are classified by the expression of specific transcription factors: ILC1 depending on T‐bet for IFN‐γ production; ILC2 depending on GATA3 for IL‐5 and IL‐13; and ILC3 depending on ROR‐γτ and AHR for IL‐17 and IL‐22. This study aimed to determine circulating ILCs in 23 patients with localized (LCL) = 7, mucocutaneous (MCL) = 10, intermediate (ICL) = 3 and diffuse (DCL) = 3 cutaneous leishmaniasis and 17 healthy controls from endemic area (EC) = 9 and non‐endemic area (HC) = 8. Results evidenced a higher proportion of ILC1 in LCL than controls and MCL. ILC2 was higher in DCL compared with controls. ILC3 s were abundant in MCL and DCL concerning controls. A prevalence ratio was calculated to approach cell plasticity: in LCL, the ratio showed a prevalence of ILC1/ILC3 (plasticity 1), in contrast to DCL, and controls, where ILC2/ILC3 (plasticity 3) is prevalent. Also, MCL and ICL showed higher ILC1/ILC2 (plasticity 2). These results suggest that ILC1 and ILC3 in LCL are associated with disease control and regulation of inflammation, while MCL and ICL are related to immunopathology and uncontrolled inflammation. In DCL, ILC2 is associated with the tolerogenic state of these patients.