Increase of NK Cells and Proinflammatory Monocytes Are Associated with the Clinical Improvement of Diffuse Cutaneous Leishmaniasis after Immunochemotherapy with BCG/Leishmania Antigens

Abstract

Diffuse cutaneous leishmaniasis (DCL) is characterized by disseminated lesions and the absence of a specific cellular immune response. Here, the immunochemotherapy outcome of a patient with DCL from Amazonian Brazil infected with Leishmania (Leishmania) amazonensis is presented. After several unsuccessful chemotherapy treatment regimens and many relapses, a monthly immunotherapy scheme of L. amazonensis PH8 plus L. (Viannia) braziliensis M2903 monovalent vaccines associated with Bacillus Calmette-Guerin (BCG) was established, one round of which also included an M2903 vaccine associated with intermittent antimonial treatment. Temporary healing of all lesions was achieved, although Leishmania skin tests were negative and interferon gamma was not detected in mononuclear cell cultures stimulated with Leishmania antigens. The frequencies of CD16 (+)CD56(+) NK cells (approximately 2x) and CD14 (+)CD16(+) proinflammatory monocytes (approximately 8x) increased in peripheral blood, and CD56 (+) lymphocytes were found infiltrating the lesions. An association between the increase of the frequency of innate immune system cells and the healing of lesions is shown, suggesting that this protocol of immunotherapy reduced the parasite load and activated NK cells and monocytes.

Interleukin 32γ (IL-32γ) is highly expressed in cutaneous and mucosal lesions of American Tegumentary Leishmaniasis patients: association with tumor necrosis factor (TNF) and IL-10

“…In patients with diffuse cutaneous leishmaniasis (DCL) caused by L. (L.) amazonensis there is a predominance of IL-10 and Th2 cytokines [59]. In this ATL form, patients do not present cellular immune response [23,60]. Then, ATL can present at the centre of the clinical spectrum localized CL, and two poles - one caused by L .…”

Anti-leishmanial effects of purified compounds from aerial parts of Baccharis uncinella C. DC. (Asteraceae)

“…Moreover, diverse works have been reported on parasite resistance and disease refratoriness after treatment with both drugs. Therefore, some chemotherapeutic measures have been performed to improve the treatment, such as the concomitant use of immunomodulatory molecules, such as BCG or imiquimoid with antimonials (Pereira et al 2009;Arevalo et al 2007). Although important results have been found with these associations, the discovering of new molecules with antileishmanial effects is urgent.…”

Leishmania (Viannia) shawi purified antigens confer protection against murine cutaneous leishmaniasis

“…In addition, these groups showed higher production of IFN-c and IL-4, together with a significant reduction in IL-2 concentration. As stated above, high production of IL-4 can inhibit and regulate the bioactivity of IFN-c; IL-2 alone can activate natural killer cells [44], which can eliminate infected cells through cytotoxicity in vivo and in vitro [8,45,46]. Therefore, the low levels of IL-2 in the F3 and F4-immunized groups could be responsible for the decrease in the number of IL2-activated NK cells, thus directing these mice to a susceptibility pole.…”