scholarly journals Repeated Sand Fly Bites of Infected BALB/c Mice Enhance the Development of Leishmania Lesions

2021 ◽  
Vol 2 ◽  
Author(s):  
Barbora Vojtkova ◽  
Daniel Frynta ◽  
Tatiana Spitzova ◽  
Tereza Lestinova ◽  
Jan Votypka ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Skin Infection ◽  
Parasite Load ◽  
Sand Fly ◽  
Parasite Development ◽  
Cutaneous Lesions ◽  
Local Skin ◽  
Vector Interaction ◽  
Phlebotomus Duboscqi ◽  
Protection Against Infection

Sand fly saliva has considerable immunomodulatory effects on Leishmania infections in mammalian hosts. Studies on several Leishmania – sand fly - host combinations have demonstrated that co-inoculation with Leishmania parasites enhances pathogenicity, while pre-exposure of hosts to sand fly bites provides significant protection against infection. However, the third scenario, the effect of sand fly saliva on parasite development in hosts infected before exposure to sand flies, remains an understudied aspect of Leishmania–host–vector interaction. Here we studied the effect of exposure of L. major-infected BALB/c mice to repeated sand fly bites. Mice infected intradermally with sand fly-derived Leishmania were repeatedly bitten by Phlebotomus duboscqi females every two weeks. The lesion development was recorded weekly for ten weeks post-infection and parasite load and distribution in various organs were tested post mortem using qPCR. Repeated sand fly bites significantly enhanced the development of cutaneous lesions; they developed faster and reached larger size than in unexposed mice. Multiple sand fly bites also increased parasites load in inoculated ears. On the other hand, the distribution of parasites in mice body and their infectiousness to vectors did not differ significantly between groups. Our study provides the first evidence that multiple and repeated exposures of infected BALB/c mice to sand fly bites significantly enhance the progress of local skin infection caused by Leishmania major and increase tissue parasite load, but do not affect the visceralization of parasites. This finding appeals to adequate protection of infected humans from sand fly bites, not only to prevent transmission but also to prevent enlarged lesions.

scholarly journals Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model

2021 ◽  
Vol 15 (3) ◽  
pp. e0009230
Author(s):  
Juliana Alcoforado Diniz ◽  
Mariana M. Chaves ◽  
Slavica Vaselek ◽  
Rubens D. Miserani Magalhães ◽  
Rafael Ricci-Azevedo ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Leishmania Major ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Capacity ◽  
Sand Fly ◽  
Parasite Development ◽  
Post Translational Modification ◽  
Phlebotomus Duboscqi ◽  
The Impact

Leishmania major is the main causative agent of cutaneous leishmaniasis in the Old World. In Leishmania parasites, the lack of transcriptional control is mostly compensated by post-transcriptional mechanisms. Methylation of arginine is a conserved post-translational modification executed by Protein Arginine Methyltransferase (PRMTs). The genome from L. major encodes five PRMT homologs, including the cytosolic protein associated with several RNA-binding proteins, LmjPRMT7. It has been previously reported that LmjPRMT7 could impact parasite infectivity. In addition, a more recent work has clearly shown the importance of LmjPRMT7 in RNA-binding capacity and protein stability of methylation targets, demonstrating the role of this enzyme as an important epigenetic regulator of mRNA metabolism. In this study, we unveil the impact of PRMT7-mediated methylation on parasite development and virulence. Our data reveals that higher levels of LmjPRMT7 can impair parasite pathogenicity, and that deletion of this enzyme rescues the pathogenic phenotype of an attenuated strain of L. major. Interestingly, lesion formation caused by LmjPRMT7 knockout parasites is associated with an exacerbated inflammatory reaction in the tissue correlated with an excessive neutrophil recruitment. Moreover, the absence of LmjPRMT7 also impairs parasite development within the sand fly vector Phlebotomus duboscqi. Finally, a transcriptome analysis shed light onto possible genes affected by depletion of this enzyme. Taken together, this study highlights how post-transcriptional regulation can affect different aspects of the parasite biology.

scholarly journals Leishmania-Derived Trimannose Modulates the Inflammatory Response To Significantly Reduce Leishmania major-Induced Lesions

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
Tara L. Grinnage-Pulley ◽  
Daniel E. K. Kabotso ◽  
Chelsea L. Rintelmann ◽  
Rajarshi Roychoudhury ◽  
Robert G. Schaut ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Parasite Load ◽  
Mannose Receptor ◽  
Lesion Size ◽  
Wild Type ◽  
Cutaneous Lesions ◽  
Content Type ◽  
Latex Beads

ABSTRACTLeishmanialipophosphoglycan (LPG) is a key virulence factor, initiating inflammation resulting in cutaneous lesions. LPG is capped by various oligosaccharides. How these glycans are recognized and how they alter the course ofLeishmaniainfection are poorly understood. Previous studies synthesized α-1,2-trimannose cap sugars on latex beads and demonstrated that C57BL/6 mice coinoculated withLeishmania majorand trimannose-coated beads produced significantly higher levels of interleukin-12p40 (IL-12p40) and other proinflammatory, type 1 cytokines than mice inoculated withL. majoralone within the first 48 h of infection. However, asL. majorinfection typically progress over weeks to months, the role of trimannose in altering disease progression over the course of infection was unknown. Wild-type mice were inoculated with either trimannose-coated or carrier (uncoated) beads, infected withL. majoralone, coinoculated with carrier beads andL. major, or coinoculated with trimannose-coated beads andL. major. Trimannose treatment ofL. major-infected mice decreased the parasite load and significantly decreased the lesion size at 14 days postinfection (p.i.) compared to results for nontreated, infected mice. Infected, trimannose-treated mice had decreased IL-12p40 and IL-10 secretion and increased interferon gamma secretion at 14 days p.i. Mannose receptor knockout (MR−/−) mice lack the ability to detect trimannose. When MR−/−mice were infected withL. majorand treated with trimannose beads, they did not have decreased lesion size.Leishmania-derived trimannose represents a novel immunomodulator that provides early type 1-skewed cytokine production to control the parasite load and alter the course of cutaneous leishmaniasis.

scholarly journals Pretreatment with Recombinant Flt3 Ligand Partially Protects against Progressive Cutaneous Leishmaniasis in Susceptible BALB/c Mice

2001 ◽  
Vol 69 (2) ◽  
pp. 673-680 ◽  
Author(s):  
Inger B. Kremer ◽  
Meetha P. Gould ◽  
Kevin D. Cooper ◽  
Frederick P. Heinzel
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
Leishmania Major ◽  
Parasite Load ◽  
Interleukin 12 ◽  
Productive Capacity ◽  
Cutaneous Lesions ◽  
Cutaneous Infections ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Dendritic cells are potent antigen-presenting cells that also produce interleukin-12 (IL-12) during innate and adaptive cellular immune responses and that thereby promote the differentiation of gamma interferon (IFN-γ)-producing Th1-type CD4+ T lymphocytes. We hypothesized that expanded dendritic-cell populations in mice pretreated with the hematopoietic cytokine Flt3L would protect against cutaneous Leishmania major infection. Pretreatment of disease-susceptible BALB/c mice with 10 μg of recombinant Flt3L (rFlt3L) for 9 to 10 days before infection increased lymph node IL-12 p40 productive capacity 20-fold compared to that of saline-injected controls. Furthermore, 9 of 22 (40.9%) rFlt3L-pretreated BALB/c mice resolved their cutaneous infections, whereas none of the 22 control BALB/c mice healed. Healed, rFlt3L-pretreated mice did not develop disease following reinfection. Flt3L pretreatment also reduced parasite numbers 1,000-fold in the cutaneous lesions at 2 weeks after infection relative to numbers in lesions of untreated controls. However, Flt3L pretreatment did not significantly alter L. major-induced IFN-γ and IL-4 production in lymph node culture at 1, 2, and 4 weeks after infection. Despite the lack of Th immune deviation, Flt3L ligand-pretreated lymph nodes expressed up to 10-fold higher levels of IL-12 p40 and inducible (type 2) nitric oxide synthase mRNA at 7 days after infection. In contrast, treatment with rFlt3L after infection failed to protect against disease despite comparable expansions of dendritic cells and IL-12 p40 productive capacity in both infected and uninfected BALB/c mice treated with rFlt3L. We conclude that rFlt3L pretreatment before infection with L. major reduces parasite load and promotes healing of cutaneous lesions without stable cytokine deviation towards a dominant Th1 cytokine phenotype.

scholarly journals Functional characterization of a salivary apyrase from the sand fly, Phlebotomus duboscqi, a vector of Leishmania major

2009 ◽  
Vol 55 (11) ◽  
pp. 1044-1049 ◽  
Author(s):  
Ryoichi Hamasaki ◽  
Hirotomo Kato ◽  
Yoshimi Terayama ◽  
Hiroyuki Iwata ◽  
Jesus G. Valenzuela
Keyword(s):  
Leishmania Major ◽  
Functional Characterization ◽  
Sand Fly ◽  
Phlebotomus Duboscqi

scholarly journals Immunomodulatory Effects of the Lutzomyia longipalpis Salivary Gland Protein Maxadilan on Mouse Macrophages

2007 ◽  
Vol 75 (5) ◽  
pp. 2359-2365 ◽  
Author(s):  
Tess M. Brodie ◽  
Matthew C. Smith ◽  
Robin V. Morris ◽  
Richard G. Titus
Keyword(s):  
Leishmania Major ◽  
Parasite Load ◽  
Sand Fly ◽  
Lutzomyia Longipalpis ◽  
No Production ◽  
Intracellular Pathogens ◽  
Tnf Α ◽  
Parasite Survival

ABSTRACT Infection with Leishmania major is enhanced when the sand fly Lutzomyia longipalpis salivary peptide maxadilan (MAX) is injected along with the parasite. Here we determined the effect that MAX has on the secretion of cytokines and nitric oxide (NO) and on parasite survival in macrophages (MΦs). The cytokines produced by MΦs can enhance a type 1 response, which will increase NO and the killing of intracellular pathogens such as L. major, or a type 2 response, leading to antibody production that is ineffective against intracellular pathogens such as L. major. A mouse macrophage cell line (RAW 264.7) was stimulated with various concentrations of MAX and lipopolysaccharide (LPS), and the supernatants were collected after 1, 2, and 3 days. Supernatants were assayed for interleukin-12p70 (IL-12p70), IL-10, IL-6, transforming growth factor β (TGF-β), NO, and tumor necrosis factor alpha (TNF-α). Our results indicate that the addition of MAX upregulates the cytokines associated with a type 2 response (IL-10, IL-6, and TGF-β) but downregulates type 1 cytokines (IL-12p70 and TNF-α) and NO. MAX was also added to L. major-infected mouse peritoneal exudate cells (PECs), and the parasite load increased significantly. The enhanced parasite load correlated with decreased NO production by PECs that were stimulated with LPS and gamma interferon in the presence of MAX. The ability of MAX to foster a type 2 response, to enhance parasite survival, and to decrease NO argues that MAX may be crucial for the early survival of Leishmania in the vertebrate host, and therefore, MAX holds considerable promise as an antigenic component for a vaccine against Leishmania.

scholarly journals Characterization of a Defensin from the Sand Fly Phlebotomus duboscqi Induced by Challenge with Bacteria or the Protozoan Parasite Leishmania major

2004 ◽  
Vol 72 (12) ◽  
pp. 7140-7146 ◽  
Author(s):  
Nathalie Boulanger ◽  
Carl Lowenberger ◽  
Petr Volf ◽  
Raul Ursic ◽  
Lucie Sigutova ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Leishmania Major ◽  
Fat Body ◽  
Protozoan Parasite ◽  
Sand Fly ◽  
Parasitic Infections ◽  
Knockout Mutants ◽  
Insect Defensin ◽  
Phlebotomus Duboscqi ◽  
Gut Pathogens

ABSTRACT Antimicrobial peptides are major components of the innate immune response of epithelial cells. In insect vectors, these peptides may play a role in the control of gut pathogens. We have analyzed antimicrobial peptides produced by the sand fly Phlebotomus duboscqi, after challenge by injected bacteria or feeding with bacteria or the protozoan parasite Leishmania major. A new hemolymph peptide with antimicrobial activity was identified and shown to be a member of the insect defensin family. Interestingly, this defensin exhibits an antiparasitic activity against the promastigote forms of L. major, which reside normally within the sand fly midgut. P. duboscqi defensin could be induced by both hemolymph or gut infections. Defensin mRNA was induced following infection by wild-type L. major, and this induction was much less following infections with L. major knockout mutants that survive poorly in sand flies, due to specific deficiencies in abundant cell surface glycoconjugates containing phosphoglycans (including lipophosphoglycan). The ability of gut pathogens to induce gut as well as fat body expression of defensin raises the possibility that this antimicrobial peptide might play a key role in the development of parasitic infections.

scholarly journals Lutzomyia longipalpis Antimicrobial Peptides: Differential Expression during Development and Potential Involvement in Vector Interaction with Microbiota and Leishmania

2021 ◽  
Vol 9 (6) ◽  
pp. 1271
Author(s):  
Erich Loza Telleria ◽  
Bruno Tinoco-Nunes ◽  
Tereza Leštinová ◽  
Lívia Monteiro de Avellar ◽  
Antonio Jorge Tempone ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Sand Fly ◽  
Parasite Development ◽  
Lutzomyia Longipalpis ◽  
Infectious Agents ◽  
Parasite Abundance ◽  
Bacteria Growth ◽  
Vector Interaction ◽  
Knockdown Effect

Antimicrobial peptides (AMPs) are produced to control bacteria, fungi, protozoa, and other infectious agents. Sand fly larvae develop and feed on a microbe-rich substrate, and the hematophagous females are exposed to additional pathogens. We focused on understanding the role of the AMPs attacin (Att), cecropin (Cec), and four defensins (Def1, Def2, Def3, and Def4) in Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. Larvae and adults were collected under different feeding regimens, in addition to females artificially infected by Leishmania infantum. AMPs’ gene expression was assessed by qPCR, and gene function of Att and Def2 was investigated by gene silencing. The gene knockdown effect on bacteria and parasite abundance was evaluated by qPCR, and parasite development was verified by light microscopy. We demonstrate that L. longipalpis larvae and adults trigger AMPs expression during feeding, which corresponds to an abundant presence of bacteria. Att and Def2 expression were significantly increased in Leishmania-infected females, while Att suppression favored bacteria growth. In conclusion, L. longipalpis AMPs’ expression is tuned in response to bacteria and parasites but does not seem to interfere with the Leishmania cycle.

scholarly journals Morphological Characterization of the Antennal Sensilla of the Afrotropical Sand Fly, Phlebotomus duboscqi (Diptera: Psychodidae)

2020 ◽  
Author(s):  
Ana Cristina Bahia ◽  
Ana Beatriz F Barletta ◽  
Luciana Conceição Pinto ◽  
Alessandra S Orfanó ◽  
Rafael Nacif-Pimenta ◽  
...  
Keyword(s):  
Morphological Characters ◽  
Morphological Characterization ◽  
Sand Fly ◽  
Antennal Sensilla ◽  
Olfactory Sensilla ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Electrophysiological Studies ◽  
Phlebotomus Duboscqi ◽  
Well Differentiated ◽  
Function Number

Abstract We investigated by scanning electron microscopy the morphology, distribution, and abundance of antennal sensilla of females Phlebotomus duboscqi sand fly, an important vector of zoonotic cutaneous leishmaniasis at Afrotropical region. Thirteen well-differentiated sensilla were identified, among six types of cuticular sensilla. The probable function of these sensillary types is discussed in relation to their external structure and distribution. Five sensillary types were classified as olfactory sensilla, as they have specific morphological characters of sensilla with this function. Number and distribution of sensilla significantly differed between antennal segments. The results of the present work, besides corroborating in the expansion of the morphological and ultrastructural knowledge of P. duboscqi, can foment future electrophysiological studies for the development of volatile semiochemicals, to be used as attractants in traps for monitoring and selective vector control of this sand fly.

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