scholarly journals Toward a Defined Anti-Leishmania Vaccine Targeting Vector Antigens

2001 ◽  
Vol 194 (3) ◽  
pp. 331-342 ◽  
Author(s):  
Jesus G. Valenzuela ◽  
Yasmine Belkaid ◽  
Mark K. Garfield ◽  
Susana Mendez ◽  
Shaden Kamhawi ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Leishmania Major ◽  
Sand Fly ◽  
Delayed Type Hypersensitivity ◽  
Salivary Proteins ◽  
Leishmania Infection ◽  
Protective Effects ◽  
Plasmid Vaccine ◽  
Targeting Vector ◽  
Leishmania Parasites

Leishmania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leishmania infection, while immunity to the saliva protects against infection as determined by coinoculation of parasites with vector salivary gland homogenates (SGHs) or by infected sand fly bites (Kamhawi, S., Y. Belkaid, G. Modi, E. Rowton, and D. Sacks. 2000. Science. 290:1351–1354). We have now characterized nine salivary proteins of Phlebotomus papatasi, the vector of Leishmania major. One of these salivary proteins, extracted from SDS gels and having an apparent mol wt of 15 kD, was able to protect vaccinated mice challenged with parasites plus SGH. A DNA vaccine containing the cDNA for the predominant 15-kD protein (named SP15) provided this same protection. Protection lasted at least 3 mo after immunization. The vaccine produced both intense humoral and delayed-type hypersensitivity (DTH) reactions. B cell–deficient mice immunized with the SP15 plasmid vaccine successfully controlled Leishmania infection when injected with Leishmania plus SGH. These results indicate that DTH response against saliva provides most or all of the protective effects of this vaccine and that salivary gland proteins or their cDNAs are viable vaccine targets against leishmaniasis.

scholarly journals Molecular Detection of Leishmania major in Hemiechinus auritus, A Potential Reservoir of Zoonotic Cutaneous Leishmaniasis in Damghan, Iran

2019 ◽  
Author(s):  
Behrad Pourmohammadi ◽  
Sadegh Mohammadi-Azni
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Natural Infection ◽  
Leishmania Infection ◽  
Northern Iran ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Potential Reservoir ◽  
Leishmania Spp ◽  
First Time ◽  
Leishmania Parasites

Background: Zoonotic cutaneous leishmaniasis caused by Leishmania major is endemic in 17 of 31 Iranian provinces. Various species of rodents have been introduced as the main reservoirs of the disease. This study was conducted to de­termine the natural infection of hedgehogs with Leishmania spp. in an endemic area of the disease, northern Iran. Methods: Fifteen long-eared hedgehogs were captured alive during 18 months study period, from Apr 2015 to Sep 2016, in Damghan City, Semnan Province, Iran. The animals were identified using apparent characteristics and to de­termine the Leishmania infection, impression smears were prepared from their ear lobes, hind feet, livers, and spleens. Micro­scopic examination and semi-nested PCR were applied to determine the infection and to identify the parasites species respectively. Results: All examined animals were identified as Hemiechinus auritus (Family: Erinaceidae). In microscopic examina­tion, 8 (53.3%) samples were shown to be infected with Leishmania parasites. The higher and lower rate of the infection was observed in the ears as well as the feet and in the liver specimens, 53.3%, and 33.3% respectively. Forty percent (6/ 15) of the samples were molecularly positive and all were identified as L. major parasites. All the examined animals in au­tumn and 50% of them in summer were shown to be infected with Leishmania parasites. Conclusion: This study demonstrated the natural infection of H. auritus with L. major for the first time in Damghan City and introduced these mammals as new potential reservoirs of ZCL in the study area.

Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis

2021 ◽  
Author(s):  
Thalia Pacheco-Fernandez ◽  
Greta Volpedo ◽  
Chaitenya Verma ◽  
Abhay R. Satoskar
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Public Health Problem ◽  
Host Immune Response ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Major Public Health Problem ◽  
Wide Range ◽  
Vector Borne ◽  
Leishmania Parasites

Leishmaniasis is a vector-borne Neglected Tropical Disease (NTD) transmitted by the sand fly and is a major public health problem worldwide. Infections caused by Leishmania clinically manifest as a wide range of diseases, such as cutaneous (CL), diffuse cutaneous (DCL), mucosal (MCL) and visceral leishmaniasis (VL). The host innate and adaptative immune responses play critical roles in the defense against leishmaniasis. However, Leishmania parasites also manipulate the host immune response for their survival and replication. In addition, other factors such as sand fly salivary proteins and microbiota also promote disease susceptibility and parasite spread by modulating local immune response. Thus, a complex interplay between parasite, sand fly and the host immunity governs disease severity and outcome. In this review, we discuss the host immune response during Leishmania infection and highlight the factors associated with resistance or susceptibility.

scholarly journals Phlebotomus papatasi sand fly salivary protein diversity and immune response potential in Egypt and Jordan populations

2019 ◽  
Author(s):  
Catherine M. Flanley ◽  
Marcelo Ramalho-Ortigao ◽  
Iliano V. Coutinho-Abreu ◽  
Rami Mukbel ◽  
Hanafi A. Hanafi ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Variability ◽  
Salivary Protein ◽  
Sand Fly ◽  
Delayed Type Hypersensitivity ◽  
Salivary Proteins ◽  
Human Populations ◽  
Phlebotomus Papatasi ◽  
Study Sites ◽  
Pharmacologically Active

AbstractPhlebotomus papatasi sand flies inject their hosts with a myriad of pharmacologically active salivary proteins to assist with blood feeding and to modulate host defenses. These salivary proteins have been studied for their role in cutaneous leishmaniasis disease outcome with different salivary proteins attenuating or exacerbating lesion size. Studies have shown that while co-administered sand fly saliva exacerbates Leishmania major infections in naïve mice, animals pre-exposed to saliva are protected, with the infection attenuated via a delayed-type hypersensitivity immune reaction. These studies highlight the potential of the salivary components to be used as a vaccine. One protein in particular, P. papatasi salivary protein 15 (PpSP15) has been intensively studied because of its ability to protect mice against Le. major challenge. The number of antigenic molecules included in vaccines is restricted thus emphasizing the role of population genetics to identify molecules, like PpSP15, that are functionally significant, conserved across populations and do not experience selection. Three distinct ecotope study sites, one in Egypt (Aswan) and two in Jordan (Swaimeh and Malka), were chosen based on their elevation, rainfall, vegetation, differing reservoir species, and the presence or absence of Le. major. The objective of this work was to analyze the genetic variability of nine of the most abundantly expressed salivary proteins including PpSP12, PpSP14, PpSP28, PpSP29, PpSP30, PpSP32, PpSP36, PpSP42, and PpSP44 and to predict their ability to elicit an immune response. Two proteins, PpSP12 and PpSP14, demonstrated low genetic variability across the three sand fly populations represented in this study, with multiple predicted MHCII epitope binding sites, identified by alleles present in the human populations from the study sites. The other seven salivary proteins revealed greater allelic variation across the same sand fly populations indicating that their use as vaccine targets may prove to be challenging.

scholarly journals Elimination of CD4+ suppressor T cells from susceptible BALB/c mice releases CD8+ T lymphocytes to mediate protective immunity against Leishmania.

1989 ◽  
Vol 169 (5) ◽  
pp. 1819-1827 ◽  
Author(s):  
J O Hill ◽  
M Awwad ◽  
R J North
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Leishmania Major ◽  
Delayed Type Hypersensitivity ◽  
Leishmania Infection ◽  
Cd8 T Lymphocytes ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

This study examined the capacity of BALB/c mice that had been depleted of T cell subpopulations to generate a protective immune response to Leishmania major. Thymectomized mice were depleted of either L3T4+ (CD4+) T lymphocytes, Ly2+ (CD8+) T lymphocytes, or both, by treatment with appropriate mAbs. It was found that susceptible mice were rendered resistant to Leishmania by an intravenous infusion of anti-L3T4 mAb. These mice generated an immune response that destroyed the parasite in the primary lesion and in visceral metastatic foci. CD4+ cell-depleted mice also acquired a capacity to mount a sustained delayed-type hypersensitivity (DTH) response to parasite antigens, indicating that DTH, per se, is not a disease-promoting mechanism in the susceptible murine host as has been suggested. Depleting BALB/c mice of CD8+, as well as CD4+ T cells, left them highly susceptible to Leishmania infection, thereby indicating that CD8+ lymphocytes are key protective cells. Our results can be interpreted as showing that the susceptibility of BALB/c mice is due to the generation of CD4+ cells that suppress either the generation or expression of CD8+ T cell-mediated antiLeishmania immunity.

scholarly journals Mast Cell Response to Leishmania mexicana and Sand Fly Salivary Proteins is Modulated by Androgens

2021 ◽  
Author(s):  
Laura Sánchez-García ◽  
Armando Perez-Torres ◽  
Samira Muñoz-Cruz ◽  
Jorge Morales-Montor ◽  
Ingeborg Becker
Keyword(s):  
Immune Response ◽  
Mast Cell ◽  
Host Immune Response ◽  
Gonadal Hormones ◽  
Sand Fly ◽  
Salivary Proteins ◽  
Leishmania Infection ◽  
Complex Fluid ◽  
The Impact ◽  
Sand Fly Vectors

Mast cells (MCs) play a crucial role during infections with Leishmania, that is transmitted through the bite of an infected sand fly that injects saliva together with the parasite. Sand fly saliva is a complex fluid that modulates the host immune response. In addition, hormonal factors modulate the host immune response, impacting the susceptibility to infections. Thus, to assess the impact of androgens and salivary proteins of sand fly vectors on the mast cell (MC) response to Leishmania infections, we infected orchiectomized male mice with the parasite in the presence or absence of sand fly salivary proteins and analyzed the inflammatory response of MCs. Our results showed a differential MC response to the parasite and to vector salivary proteins in mice deprived of gonadal hormones, as compared to sham-operated mice. Orchidectomy induced a different pattern of activation in MC of animals infected with Leishmania and vector-salivary proteins. Our results show that during Leishmania infection, androgens modulate the innate immunity response against the parasite and salivary proteins of the sand fly vector.

DETECTION OF LEISHMANIA INFECTION IN STRAY DOGS IN HUMAN LEISHMANIASIS ENDEMIC AREA IN MYMENSINGH DISTRICT WITH ITS POSSIBLE PUBLIC HEALTH SIGNIFICANCE IN BANGLADESH

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
M. A. Hossen
Keyword(s):  
Visceral Leishmaniasis ◽  
Asymptomatic Carrier ◽  
Asymptomatic Infection ◽  
Reservoir Host ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Endemic Region ◽  
Stray Dogs ◽  
Human Leishmaniasis ◽  
Strip Test

Background: Leishmaniasis is primarily caused by two species of Leishmania (L. donovani and L. infantum) of which clinical infection with L. infantum has been recognized in both humans and dogs as zoonotic disease with dogs as the main reservoir hosts in the Mediterranean, the Middle East, Asia and South America. Although L. donovani has been associated with both clinical and asymptomatic infection in humans but it is still associated with asymptomatic infection in dogs in Indian sub-continent without any evidence of zoonotic infection. Objectives: The objective of this research was to investigate the potentiality of dog as reservoir host for visceral leishmaniasis in the human leishmaniasis endemic regions in Bangladesh. Materials and Methods: A total of 20 stray dogs in the human VL endemic areas of Mymensingh district were captured for the detection VL during the period of November 2010 to May 2011. The dipstick test rK39 (Bios International; n = 20), Giemsa’s stained impression smears of liver and spleen (n = 6) and PCR with the tissue of liver and spleen (n = 6) were tested as per manufacturer instructions and conventional standard methods. Results: Out of 20 stray dogs examined, 4 (20.0%) were positive for L. donovani infection with rK39 strip test. Of the six randomly selected dogs tested with Modified Giemsa’s stained of impression smears of spleen and liver showed 2 (33.33%) positive whereas PCR technique detected 5 (83.33%) positive for L. donovani. Results of PCR showed 145bp amplicon, specific for L. donovani infection in 83.33% stray dogs. Conclusions: This study reveals that a high percentage of L. donovani asymptomatic carrier infections occur in dogs and evidence indicates that dogs and humans may potentially serve as a source of infection to sand fly vectors and accordingly dogs can be recognized as a probable animal reservoir for the Leishmania infection in the endemic region in Bangladesh. However, further studies are required to determine the ability of dogs to transmit the L. donovani to the vector sand fly in nature and its evidence on ‘One Health’ perspectives. Keywords: Visceral leishmaniasis, Endemic region, Stray dogs, rK39 strip test, Giemsa’s stained liver and spleen impression smears, PCR, Reservoir host, Mymensingh

scholarly journals Isolation and Molecular Typing of Leishmania infantum from Phlebotomus perfiliewi in a Re-Emerging Focus of Leishmaniasis, Northeastern Italy

2019 ◽  
Vol 7 (12) ◽  
pp. 644
Author(s):  
Mattia Calzolari ◽  
Elena Carra ◽  
Gianluca Rugna ◽  
Paolo Bonilauri ◽  
Federica Bergamini ◽  
...  
Keyword(s):  
Leishmania Infection ◽  
Sand Flies ◽  
Repetitive Region ◽  
Microsatellite Typing ◽  
Increasing Trend ◽  
Northeastern Italy ◽  
Emilia Romagna Region ◽  
Phlebotomus Perfiliewi ◽  
Leishmania Parasites

Visceral leishmaniasis (VL) caused by Leishmania (L.) infantum is a public health threat in the Emilia-Romagna region, northeastern Italy, but its epidemiology has not been fully elucidated in this area. The objective of this study was to characterize Leishmania infection in sand flies collected in a re-emerging focus of VL in the Bologna province. During the summer of 2016, 6114 sand flies were collected, identified, and tested for Leishmania detection. Of the identified sand flies, 96.5% were Phlebotomus (P.) perfiliewi and 3.5% were P. perniciosus. Detected parasites were characterized by biomolecular methods (multilocus microsatellite typing and characterization of repetitive region on chromosome 31), and quantified by real-time PCR. The prevalence of Leishmania infection in individually-tested P. perfiliewi sand flies varied from 6% to 10% with an increasing trend during the season. Promastigotes of L. infantum were isolated by dissection in one P. perfiliewi female; the isolated strain (Lein-pw) were closely related to Leishmania parasites from VL cases in northeastern Italy, but differed from strains isolated in dogs from the same area. Our findings strongly support the vector status of P. perfiliewi for human VL in the study area.

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