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 Phlebotomus papatasi sand fly predicted salivary protein diversity and immune response potential based on in silico prediction in Egypt and Jordan populations

2020 ◽  
Vol 14 (7) ◽  
pp. e0007489
Author(s):  
Catherine M. Flanley ◽  
Marcelo Ramalho-Ortigao ◽  
Iliano V. Coutinho-Abreu ◽  
Rami Mukbel ◽  
Hanafi A. Hanafi ◽  
...  
Keyword(s):  
Immune Response ◽  
In Silico ◽  
Salivary Protein ◽  
Sand Fly ◽  
Phlebotomus Papatasi ◽  
In Silico Prediction ◽  
Protein Diversity

Pemphigus foliaceus and sand fly bites: assessing the humoral immune response to the salivary proteins maxadilan and LJM11

2020 ◽  
Vol 183 (5) ◽  
pp. 958-960 ◽  
Author(s):  
S. Vernal ◽  
N.A. De Paula ◽  
V.R. Bollela ◽  
E.A. Lerner ◽  
A.M. Roselino
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Sand Fly ◽  
Salivary Proteins ◽  
Pemphigus Foliaceus ◽  
Humoral Immune

Genetic Variability of Sand Fly Phlebotomus papatasi Populations (Diptera: Psychodidae) Originating from the West Bank, Palestine

2007 ◽  
Vol 4 (6) ◽  
pp. 425-434 ◽  
Author(s):  
Omar Hamarsheh ◽  
Sameer Barghouthi . ◽  
Amer Al-Jawabreh . ◽  
Abdel Baset Zayed . ◽  
Kifaya Azmi . ◽  
...  
Keyword(s):  
Genetic Variability ◽  
West Bank ◽  
Sand Fly ◽  
Phlebotomus Papatasi ◽  
The West

Salivary glands of the sand fly Phlebotomus papatasi contain pharmacologically active amounts of adenosine and 5′-AMP

1999 ◽  
Vol 202 (11) ◽  
pp. 1551-1559 ◽  
Author(s):  
J.M. Ribeiro ◽  
O. Katz ◽  
L.K. Pannell ◽  
J. Waitumbi ◽  
A. Warburg
Keyword(s):  
Mass Spectrometry ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Blood Meal ◽  
Protein Phosphatase ◽  
Sand Fly ◽  
Phlebotomus Papatasi ◽  
Pharmacologically Active ◽  
Phosphatase Substrate ◽  
Allosteric Modification

Salivary gland homogenates of the sand fly Phlebotomus papatasi contain large amounts of adenosine and 5′-AMP, of the order of 1 nmol per pair of glands, as demonstrated by liquid chromatography, ultraviolet spectrometry, mass spectrometry and bioassays. These purines, 75–80 % of which are secreted from the glands following a blood meal, have vasodilatory and anti-platelet activities and probably help the fly to obtain a blood meal. Salivary 5′-AMP is also responsible for the previously reported protein phosphatase inhibitor in the salivary glands of P. papatasi, which is shown to be artifactual in nature as a result of allosteric modification by AMP of the phosphatase substrate used (phosphorylase a).

scholarly journals CRISPR/Cas9 Mutagenesis in Phlebotomus papatasi: the Immune Deficiency Pathway Impacts Vector Competence for Leishmania major

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Isabelle Louradour ◽  
Kashinath Ghosh ◽  
Ehud Inbar ◽  
David L. Sacks
Keyword(s):  
Immune Deficiency ◽  
Immune Response ◽  
Leishmania Major ◽  
Vector Competence ◽  
Targeted Mutagenesis ◽  
Sand Fly ◽  
Sand Flies ◽  
Phlebotomus Papatasi ◽  
Content Type ◽  
Imd Pathway

ABSTRACT Sand flies are the natural vectors for the Leishmania species that produce a spectrum of diseases in their mammalian hosts, including humans. Studies of sand fly/Leishmania interactions have been limited by the absence of genome editing techniques applicable to these insects. In this report, we adapted CRISPR (clustered regularly interspaced palindromic repeat)/Cas9 (CRISPR-associated protein 9) technology to the Phlebotomus papatasi sand fly, a natural vector for Leishmania major, targeting the sand fly immune deficiency (IMD) pathway in order to decipher its contribution to vector competence. We established a protocol for transformation in P. papatasi and were able to generate transmissible null mutant alleles for Relish (Rel), the only transcription factor of the IMD pathway. While the maintenance of a homozygous mutant stock was severely compromised, we were able to establish in an early generation their greater susceptibility to infection with L. major. Flies carrying different heterozygous mutant alleles variably displayed a more permissive phenotype, presenting higher loads of parasites or greater numbers of infective-stage promastigotes. Together, our data show (i) the successful adaptation of the CRISPR/Cas9 technology to sand flies and (ii) the impact of the sand fly immune response on vector competence for Leishmania parasites. IMPORTANCE Sand flies are the natural vectors of Leishmania parasites. Studies of sand fly/Leishmania interactions have been limited by the lack of successful genomic manipulation of these insects. This paper shows the first example of successful targeted mutagenesis in sand flies via adaptation of the CRISPR/Cas9 editing technique. We generated transmissible null mutant alleles of relish, a gene known to be essential for the control of immune response in other insects. In addition to the expected higher level of susceptibility to bacteria, the mutant flies presented higher loads of parasites when infected with L. major, showing that the sand fly immune response impacts its vector competence for this pathogen.

Human immune response to salivary proteins of wild-caught Phlebotomus papatasi

2016 ◽  
Vol 115 (9) ◽  
pp. 3345-3355 ◽  
Author(s):  
Rami M. Mukbel ◽  
Rehab H. Khasharmeh ◽  
Nawal S. Hijjawi ◽  
Mohammed S. Khalifeh ◽  
Ma’mon M. Hatmal ◽  
...  
Keyword(s):  
Immune Response ◽  
Salivary Proteins ◽  
Phlebotomus Papatasi ◽  
Human Immune Response ◽  
Human Immune

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 Immunity to Distinct Sand Fly Salivary Proteins Primes the Anti-Leishmania Immune Response towards Protection or Exacerbation of Disease

2008 ◽  
Vol 2 (4) ◽  
pp. e226 ◽  
Author(s):  
Fabiano Oliveira ◽  
Phillip G. Lawyer ◽  
Shaden Kamhawi ◽  
Jesus G. Valenzuela
Keyword(s):  
Immune Response ◽  
Sand Fly ◽  
Salivary Proteins
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