Sand fly saliva enhances Leishmania amazonensis infection by modulation interleukin-10 production

被引:96
作者
Norsworthy, NB
Sun, JR
Elnaiem, D
Lanzaro, G
Soong, L
机构
[1] Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
[2] Univ Texas, Med Branch, Dept Pathol, Ctr Biodefense & Emerging Infect Dis,Sealy Ctr Va, Galveston, TX 77555 USA
[3] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA
关键词
D O I
10.1128/IAI.72.3.1240-1247.2004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
After transmission through the bite of female sand flies, Leishmania spp. can cause a broad spectrum of disease manifestations collectively known as leishmaniases. L. amazonensis is endemic in South America, where it causes cutaneous, diffuse cutaneous, and visceral leishmaniasis. In this study, we have provided evidence that salivary gland extracts (SGE) of Lutzomyia longipalpis enhances L. amazonensis infection. BALB/c mice infected intradermally in the ear with 10(5) metacyclic promastigotes of L. amazonensis together with SGE (equivalent to 0.5 gland) showed an early onset of disease and larger lesions that contained similar to3-log-units more parasites than did controls. To determine the potential mechanism underlying this enhancement, we assessed cytokine production via reverse transcriptase PCR and enzyme-linked immunosorbent assay. Mice coinjected with parasites and SGE displayed higher levels of interleukin-10 (IL-10) mRNA in the ear tissues, as well as higher levels of IL-10 in supernatants of restimulated draining lymph node (LN) cells, than did controls. Flow cytometric analysis revealed high frequencies of IL-10-producing CD4(+) and CD8(+) T cells in the draining LN of mice coinjected with the parasite and SGE. In addition, we examined bone marrow derived-macrophage cultures and detected increased IL-10 but decreased nitric oxide (NO) production in cells exposed to SGE prior to infection with L. amazonensis. Together, these results imply that the sand fly saliva facilitates Leishmania evasion of the host immune system by modulating IL-10 production.
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页码:1240 / 1247
页数:8
相关论文
共 74 条
[1]   THE CHEMOTACTIC EFFECT OF PHLEBOTOMUS-DUBOSCQI (DIPTERA, PSYCHODIDAE) SALIVARY-GLAND LYSATES TO MURINE MONOCYTES [J].
ANJILI, CO ;
MBATI, PA ;
MWANGI, RW ;
GITHURE, JI ;
OLOBO, JO ;
ROBERT, LL ;
KOECH, DK .
ACTA TROPICA, 1995, 60 (02) :97-100
[2]   LEISHMANIASIS IN BAHIA, BRAZIL - EVIDENCE THAT LEISHMANIA-AMAZONENSIS PRODUCES A WIDE SPECTRUM OF CLINICAL-DISEASE [J].
BARRAL, A ;
PEDRALSAMPAIO, D ;
GRIMALDI, G ;
MOMEN, H ;
MCMAHONPRATT, D ;
DEJESUS, AR ;
ALMEIDA, R ;
BADARO, R ;
BARRALNETTO, M ;
CARVALHO, EM ;
JOHNSON, WD .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1991, 44 (05) :536-546
[3]   ISOLATION OF LEISHMANIA-MEXICANA-AMAZONENSIS FROM THE BONE-MARROW IN A CASE OF AMERICAN VISCERAL LEISHMANIASIS [J].
BARRAL, A ;
BADARO, R ;
BARRALNETTO, M ;
GRIMALDI, G ;
MOMEM, H ;
CARVALHO, EM .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1986, 35 (04) :732-734
[4]   TRANSFORMING GROWTH-FACTOR-BETA IN LEISHMANIAL INFECTION - A PARASITE ESCAPE MECHANISM [J].
BARRALNETTO, M ;
BARRAL, A ;
BROWNELL, CE ;
SKEIKY, YAW ;
ELLINGSWORTH, LR ;
TWARDZIK, DR ;
REED, SG .
SCIENCE, 1992, 257 (5069) :545-548
[5]   Development of a natural model of cutaneous leishmaniasis:: Powerful effects of vector saliva and saliva preexposure on the long-term outcome of Leishmania major infection in the mouse ear dermis [J].
Belkaid, Y ;
Kamhawi, S ;
Modi, G ;
Valenzuela, J ;
Noben-Trauth, N ;
Rowton, E ;
Ribeiro, J ;
Sacks, DL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (10) :1941-1953
[6]   A natural model of Leishmania major infection reveals a prolonged "silent" phase of parasite amplification in the skin before the onset of lesion formation and immunity [J].
Belkaid, Y ;
Mendez, S ;
Lira, R ;
Kadambi, N ;
Milon, G ;
Sacks, D .
JOURNAL OF IMMUNOLOGY, 2000, 165 (02) :969-977
[7]   The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure [J].
Belkaid, Y ;
Hoffmann, KF ;
Mendez, S ;
Kamhawi, S ;
Udey, MC ;
Wynn, TA ;
Sacks, DL .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (10) :1497-1506
[8]   Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity [J].
Bogdan, C ;
Röllinghoff, M ;
Diefenbach, A .
CURRENT OPINION IN IMMUNOLOGY, 2000, 12 (01) :64-76
[9]   MACROPHAGE DEACTIVATION BY INTERLEUKIN-10 [J].
BOGDAN, C ;
VODOVOTZ, Y ;
NATHAN, C .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 174 (06) :1549-1555
[10]   High intralesional interleukin-10 messenger RNA expression in localized cutaneous Leishmaniasis is associated with unresponsiveness to treatment [J].
Bourreau, E ;
Prévot, G ;
Gardon, J ;
Pradinaud, R ;
Launois, P .
JOURNAL OF INFECTIOUS DISEASES, 2001, 184 (12) :1628-1630