Dichotomy of the human T cell response to Leishmania antigens. II. Absent or Th2-like response to gp63 and Thl-like response to lipophosphoglycan- associated protein in cells from cured visceral leishmaniasis patients

Abstract

SUMMARY The T cell response to different Leishmania donovani aniigens was investigated using peripheral blood mononuciear cells (PBMC) from Kenyans cured of visceral leishmaniasis and non‐exposed Danes. Crude promastigote and amastigote antigens both induced proliferation and interferon‐gamma (IFN‐γ) production in PBMC from cured patients, while cells from non‐exposed donors gave weak responses. A similar pattern was indticed by lipophosphoglycan‐associated protein (LPGAP). By contrast, the major surface protease of Leishmania. gp63, induced only a weak proliferative response without IFN‐γ production in five of 17 samples from cured patients. Four of the five responding cultures produced IL‐4, i.e. the response to this antigen was of the Th2 type. Furthermore, sera from acutely ill visceral leishmaniasis patients contained high levels of IgG antibodies to gp63. The Th2‐tike response to gp63 in patients cured of visceral leishmaniasis differs from the Thl‐like response to the same antigen observed in patients cured of cutaneous leishmaniasis.

IL-27 enhances Leishmania amazonensis infection via ds-RNA dependent kinase (PKR) and IL-10 signaling

“…To date, a plethora of cytokines has been described to influence the establishment or replication of Leishmania (Kaye and Scott, 2011;Sacks and Noben-Trauth, 2002;Cummings et al, 2010;Locksley et al, 1987;Kurtzhals et al, 1994). In this study, we show that Interleukin (IL)-27 directly promotes the replication of Leishmania amazonensis in both human and murine macrophages, thus unveiling a novel biological function for this cytokine in the context of the biology of the infection by protozoan parasites.…”

Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis

“…Even though peripheral T cells may only to some extent reflect the situation in infected tissue, the present finding ofThl-like responses in individuals with a past history of self-healing CL is in striking contrast to the mixed Thl-and Th2-like response to /,. donovani observed in individuals eured from visceral Icishmaniasis [33,34]. Future investigations tnay clarify why human CL results in Thl-like responses, whereas human viseeral JeishmaniasJs can induce a mixed response.…”

Identifying vaccine targets for anti-leishmanial vaccine development

“…In addition there are abundant GPI-anchored glycosylinositolphospholipids (GIPLs) that do not attach protein to them but form a densely packed layer onto parasite surface. LPG is the most important and complex glycophospholipid that consists of type-2 anchor (Man_1–3Man_1–4GlcN_1–6PI motif) attached to a phosphosaccharide-repeat domain, which undergoes species-specific side-chain modifications with a capping of neutral oligosaccharide [126]. …”