The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major

Kemp, Michael

doi:10.1016/s0928-8244(98)00015-7

Cited by 13 publications

(17 citation statements)

References 17 publications

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“…This protein is involved in parasite attachment and invasion of host macrophages via interactions with the complement receptor 3 (CR3) (Kedzierski et al 2004). Previous studies indicated that the PSA-2 complex proteins are strong inducers of Th1 immune response in humans (Handman et al 1995 b ;Kemp et al 1998) and protection against virulent challenge in the mouse experimental infection (Handman et al 1995 b). PSA-2 is a family of glycosylinositol phospholipid-anchored polypeptides which are differentially expressed during the parasite life cycle (Handman et al 1995 a ;Jimenez-Ruiz et al 1998) : some members of this family are essentially expressed by Leishmania amastigotes suggesting that they may exert their function during the intercellular stage of the parasite.…”

Section: Discussionmentioning

confidence: 99%

Approaches for the identification of potential excreted/secreted proteins ofLeishmania majorparasites

et al. 2006

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Leishmania parasites are able to survive in host macrophages despite the harsh phagolysosomal vacuoles conditions. This could reflect, in part, their capacity to secrete proteins that may play an essential role in the establishment of infection and serve as targets for cellular immune responses. To characterize Leishmania major proteins excreted/secreted early after promastigote entry into the host macrophage, we have generated antibodies against culture supernatants of stationary-phase promastigotes collected 6 h after incubation in conditions that partially reproduce those prevailing in the parasitophorous vacuole. The screening of an L. major cDNA library with these antibodies led us to isolate 33 different cDNA clones that we report here. Sequence analysis revealed that the corresponding proteins could be classified in 3 groups: 9 proteins have been previously described as excreted/secreted in Leishmania and/or other species; 11 correspond to known proteins already characterized in Leishmania and/or other species although it is unknown whether they are excreted/secreted and 13 code for unknown proteins. Interestingly, the latter are transcribed as shown by RT-PCR and some of them are stage regulated. The L. major excreted/secreted proteins may constitute putative virulence factors, vaccine candidates and/or new drug targets.

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Section: Discussionmentioning

confidence: 99%

Approaches for the identification of potential excreted/secreted proteins ofLeishmania majorparasites

et al. 2006

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“…CL is often a selfhealing disease; however, persistent lesion lasting for several years is known (nonhealing form). Immune responses to Leishmania have been studied mostly in subjects with active lesions and/or those who had recovered from infection with Old or New World Leishmania parasites (6,(12)(13)(14)(15)24). There are few reports on the immune status of nonhealing patients, particularly those infected with L. major (25).…”

Section: Discussionmentioning

confidence: 99%

“…Concerning the key role of cytokines, we were interested in defining the immune response of nonhealing patients and comparing it with that of individuals who had recovered from infection and patients who were newly infected. Immune response to different species of Leishmania have been studied mostly in subjects with active lesions and/or patients who had recovered (6,(12)(13)(14)(15)24). There are few reports on the immune status of nonhealing patients, particularly those infected with L. major.…”

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confidence: 99%

Comparison of the Immune Profile of Nonhealing Cutaneous Leishmaniasis Patients with Those with Active Lesions and Those Who Have Recovered from Infection

et al. 2000

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Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is often a self-healing disease; however, persistent nonhealing forms are also known. In the present study, we have described cell-mediated immune responses in nonhealing patients by measuring T-cell proliferation, cytokine production, and phenotypic characterization of these cells. The responses were compared with those of patients with active lesions, patients who had recovered from infection, and healthy controls. Peripheral blood mononuclear cells from patients with active lesions and recovered donors proliferated vigorously and produced Th1-type cytokine when stimulated with L. major antigens, whereas in nonhealing patients the proliferative responses were significantly lower and showed a Th2-type response to Leishmania antigens. Interleukin-10 (IL-10) production was not a feature of L. major stimulation. Flow cytometric analysis revealed that L. major antigen induced proliferation of the CD4-positive population and that these cells were the major source of gamma interferon and IL-4. These results show a distinct dichotomy in the cytokine response to L. major infection.Leishmania major is the causative agent of zoonotic cutaneous leishmaniasis (CL) and affects millions of people in many parts of the world (30). The disease is prevalent in many areas of Iran. Hyperendemic foci of zoonotic CL in northeastern, southwestern, and central parts of Iran have been reported (9, 10, 31). The most common presentation of CL is one or a few skin lesions, which often heal spontaneously and leave a depressive scar. However, a rare presentation of infection, involving persistent lesions, is also known. These so-called nonhealing forms last for several years and do not respond to conventional chemotherapies. Patients are mostly from areas of hyperendemic infection and include some of the soldiers who were immunized with virulent parasites (leishmanization) during the Iraq war against Iran. Some of these patients experience periods of remission and reactivation at the site of inoculation, and others suffer from chronic lesion for several years.Extensive studies with experimental models have shown that the outcome of infection is critically dependent on the activation of one of the two subsets of CD4 T cells, Th1 and Th2 (26). Gamma interferon (IFN-␥), secreted by Th1 cells, is the most potent macrophage-activating cytokine leading to host resistance to infection with Leishmania parasites (27, 29), whereas interleukin-4 (IL-4), secreted by Th2 cells, is associated with down-modulation of IFN-␥-mediated macrophage activation (1, 17). However, in human cutaneous leishmaniasis, a clear functional dichotomy in CD4 T cells has not definitely been documented. Concerning the key role of cytokines, we were interested in defining the immune response of nonhealing patients and comparing it with that of in...

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“…However, immunization with recombinant PSA-2 expressed in L. mexicana promastigotes provided excellent protection against L. major challenge infection [137]. In vitro stimulation of peripheral blood mononuclear cells, from previously exposed cutaneous leishmaniasis patients, with PSA-2 produced high amounts of IFN-γ and TNF-β, and little IL-4, thereby showing a Th1 cytokine pattern [139].…”

Section: Psa-2/gp46/m-2mentioning

confidence: 99%

Vaccine candidates for leishmaniasis: A review

Nagill

Kaur

2011

International Immunopharmacology

111

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The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major

Cited by 13 publications

References 17 publications

Approaches for the identification of potential excreted/secreted proteins ofLeishmania majorparasites

Approaches for the identification of potential excreted/secreted proteins ofLeishmania majorparasites

Comparison of the Immune Profile of Nonhealing Cutaneous Leishmaniasis Patients with Those with Active Lesions and Those Who Have Recovered from Infection

Vaccine candidates for leishmaniasis: A review

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