Salivary gland material from the sand fly Lutzomyia longipalpis has an inhibitory effect on macrophage function in vitro

Theodos, Cynthia M.; Titus, Richard G.

doi:10.1111/j.1365-3024.1993.tb00634.x

Cited by 98 publications

(61 citation statements)

References 30 publications

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“…Although some Lu. longipalpis salivary components present immunomodulatory and anti-inflammatory properties [7,21,31], the development of DTH-like reactions to Lu. longipalpis SGS exposure in experimental models [25] and in individuals from endemic areas [19] suggests that these components elicit host-specific IR.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, in vitro experiments demonstrate that SGS from Lu. longipalpis [20,21] or other sand fly species [22] modulates pro-inflammatory cytokine production as well as co-stimulatory molecule expression in human antigen-presenting cells [23], suggesting that SGS can impair host response against Leishmania. Although these data suggest that saliva components influence IR in vitro as well as in vivo in Leishmania-infected patients, the response to saliva in uninfected subjects in vivo has not been evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis

et al. 2007

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Experiments in animals verified that phlebotomine saliva enhances Leishmania infection, and vaccination with saliva prevents disease. We have shown that individuals from an endemic area of visceral leishmaniasis displayed robust antibody responses to saliva from the vector Lutzomyia longipalpis, which correlated with anti-parasite cellmediated immunity. Here, we explored human anti-saliva responses following exposure to sand flies, using an in vivo bite model in which normal volunteers were exposed four times to 30 laboratory-reared Lu. longipalpis. Following the third exposure, normal volunteers developed diverse dermatological reactions at the site of insect bite. Serum from normal volunteers displayed high levels of anti-salivary gland sonicate IgG1, IgG4 and IgE as well as several salivary gland proteins. Furthermore, following in vitro stimulation with salivary gland sonicate, there was an increased frequency of CD4 + CD25 + and CD8 + CD25 + T cells as well as IFN-c and IL-10 synthesis. Strikingly, 1 year after the first exposure, PBMC from the volunteers displayed recall IFN-c responses that correlated with a significant reduction in infection rates using a macrophage-lymphocyte autologous culture. Together, these data suggest that human immunization against sand fly saliva is feasible and recall responses are obtained even 1 year after exposure, opening perspectives for vaccination in man.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis

et al. 2007

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“…We did not investigate the mechanisms by which sand fly saliva inhibited release of chemotactic mediators, but it could be a consequence of macrophage inhibition of antigen presentation and also of the activity of CD4 + T-lymphocytes. This hypothesis is supported by studies that demonstrated that in a murine resistance model to leishmaniasis, the co-injection of SGE with Leishmania inhibits activation of T cells [50], as well as the oxidative burst [51], NO production [21,52] and antigen presentation [20] by macrophages. Furthermore, saliva also inhibited production of the proinflammatory cytokines, TNF-a, IFN-c and IL-12, enhancing the release of the anti-inflammatory mediators IL-4 and IL-10, in the focus of the Leishmania infection [23-25, 53, 54].…”

mentioning

confidence: 80%

Effect of salivary gland extract ofLeishmania vector,Lutzomyia longipalpis, on leukocyte migration in OVA-induced immune peritonitis

Monteiro¹,

Nogueira²,

Souza³

et al. 2005

Eur. J. Immunol.

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Salivary gland extracts (SGE) from Lutzomyia longipalpis potentate L. major infection by inducing a Th2 immune response. However, the effect of SGE on the effector phase of immune response is not known. Herein, we demonstrate that SGE inhibited neutrophil migration in ovalbumin (OVA)-induced peritonitis in immunized mice. SGE pretreatment of mice inhibited OVA-induced CD4 + and CD8 + T lymphocyte migration. The OVA-induced production of TNF-a, IL-1b and leukotriene B4 (LTB 4 ), neutrophil chemotactic mediators in this model, were inhibited by SGE. On the other hand, SGE enhanced production of IL-10 and IL-4. In naive mice, SGE also blocked LTB 4 -induced neutrophil migration, but not that induced fMLP. Moreover, co-incubation of LTB 4 (but not fMLP, TNF-a and MIP-1a) with SGE inhibited the ability of LTB 4 to induce neutrophil migration in vivo and in vitro. Altogether, the results suggest that SGE has anti-inflammatory properties that are associated with inhibition of TNF-a and LTB 4 production and/or with the neutrophil chemotactic activity of LTB 4 . The effectiveness of SGE in inhibiting neutrophil migration and inflammatory mediators release in a Th1 immune inflammatory response model reinforces the need for isolation of the compounds responsible for these activities, which could be used as prototypes for the development new anti-inflammatory drugs. IntroductionParticipation of vector saliva in disease transmission has long been recognized. Saliva inoculated during blood feeding modulates the immune response allowing the infection to become established [1][2][3]. On the other hand, anti-vector saliva immunity may protect the host against some vector-borne diseases [4][5][6][7]. In leishmaniasis, there is evidence that the saliva of the vectors Lutzomyia and Phlebotomus contains substances with immunosuppressor, vasodilatator, anti-platelet and anticlotting activities [8][9][10][11][12][13]. In addition to increasing the hemorrhagic pool where sand flies feed [8,14], salivary components also induce host immunosuppression, which is fundamental for the establishment of Leishmania infection [10,[15][16][17][18][19] production and antigen presentation by infected macrophages [20][21][22]. Furthermore, they inhibit Th1 induction, enhancing the Th2-type response with an increase of IL-4 and IL-10 in the infection [23][24][25]. A predominance of the Th1 response has been reported in several inflammatory diseases, including rheumatoid arthritis, Crohn's disease, glomerulonephritis, and immune vasculitis [26][27][28][29]. The participation of neutrophils in the pathogenesis of tissue lesions in these diseases has long been recognized [30][31][32][33]. These cells are important sources of substances that promote tissue damage, such as reactive oxygen and nitrogen species, lysosomal enzymes and metalloproteases [34,35]. Indeed, the efficacy of the so-called disease modifying anti-inflammatory drugs in several inflammatory diseases, such as rheumatoid arthritis is usually associated with their ability to decrease neutro...

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“…Studies evaluating the effect of mosquito saliva on the immune response began relatively recently (Bissonnette et al 1993, Cross et al 1994, following the discovery that sand fly saliva enhanced infections with Leishmania major (Ribeiro 1989b, Theodos andTitus 1993). Early work described a factor in Ae.…”

Section: Modulation Of the Vertebrate Immune Response By Mosquito Salivamentioning

confidence: 99%

“…As described above, components of mosquito saliva have immunomodulatory activity, and thus, as a consequence, mosquito saliva can affect the anti-viral immune response and virus pathogenesis. Indeed, enhanced infection attributable to components of arthropod saliva is an accepted phenomenon, particularly with agents transmitted by ticks and sand flies (Cupp et al 1998, Edwards et al 1998, Limesand et al 2000, Nuttall and Labuda 2004, Theodos and Titus 1993. For example, when Leishmania major is inoculated with salivary gland extracts of sand flies, parasite burden, lesion size, and disease outcome are all amplified (Titus and Ribeiro 1988).…”

Section: Mosquito Associated Potentiation Of Arbovirus Transmission Amentioning

confidence: 99%

The enhancement of arbovirus transmission and disease by mosquito saliva is associated with modulation of the host immune response

Schneider

Higgs

2008

Transactions of the Royal Society of Tropical Medicine and Hygi

227

198

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SUMMARYArthropod-borne viruses have emerged as a major human health concern. Viruses transmitted by mosquitoes are the cause of the most serious and widespread arbovirus diseases worldwide and are ubiquitous in both feral and urban settings. Arboviruses, including dengue and West Nile virus are injected into vertebrates within mosquito saliva during mosquito feeding. Mosquito saliva contains anti-haemostatic, anti-inflammatory and immunomodulatory molecules that facilitate the acquisition of a blood-meal. Collectively, studies investigating the effects of mosquito saliva on the vertebrate immune response suggest that at high concentrations salivary proteins are immmunosuppressive, whereas lower concentrations modulate the immune response; specifically, T H 1 and antiviral cytokines are down-regulated, while T H 2 cytokines are unaffected or amplified. As a consequence, mosquito saliva can impair the anti-viral immune response thus affecting viral infectiousness and host survival. Mounting evidence suggests that this is a mechanism whereby arbovirus pathogenicity is enhanced. In a range of disease models, including various hosts, mosquito species, and arthropodborne viruses, mosquito saliva and/or feeding is associated with a potentiation of virus infection. Compared to arbovirus infection initiated in absence of the mosquito or its saliva, infection including mosquito saliva leads to an increase in virus transmission, host susceptibility, viraemia, disease progression, and mortality.Keywords arthropod-borne virus; mosquito saliva; immunomodulation; disease enhancement Most arthropod-borne (arbo)viruses of public health significance are mosquito-borne, and thus transmitted to vertebrates via the feeding of an infected mosquito. For a mosquito to

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Salivary gland material from the sand fly Lutzomyia longipalpis has an inhibitory effect on macrophage function in vitro

Cited by 98 publications

References 30 publications

Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis

Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis

Effect of salivary gland extract ofLeishmania vector,Lutzomyia longipalpis, on leukocyte migration in OVA-induced immune peritonitis

The enhancement of arbovirus transmission and disease by mosquito saliva is associated with modulation of the host immune response

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