Complement C3 is Required for the Progression of Cutaneous Lesions and Neutrophil Attraction in Leishmania Major Infection

Overview

Journal Med Microbiol Immunol

Specialty Allergy & Immunology

Date 2004 Sep 21

PMID 15378355

Citations 11

Authors

Thomas Jacobs

Jorg Andra

Iris Gaworski

Sebastian Graefe

Katja Mellenthin

Manfred Kromer

Roman Halter

Jurgen Borlak

Joachim Clos

Affiliations

Soon will be listed here.

Abstract

To elucidate the role of complement-mediated uptake in Leishmania major infection in vivo, transgenic BALB/c mice that express the cobra venom factor (CVF) under control of the alpha1-antitrypsin promoter were infected. CVF expression in these mice leads to a continuous activation and subsequent consumption of complement C3 in the serum. In contrast to susceptible non-transgenic BALB/c mice, CVF-transgenic mice are highly resistant to L. major infection and show a significantly reduced parasite dissemination. Transient depletion of C3 in wild-type BALB/c mice delays progression of lesions for some days. Both CVF-transgenic and non-transgenic mice exhibit similar T cell responses upon infection. However, in CVF-transgenic mice, no infiltration of neutrophils, which were the prominent infiltrating cells at the site of infection in normal susceptible mice, could be detected. We conclude that C3 cleavage is required for the attraction of neutrophils that participate in parasite dissemination.

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References

Aga E, Katschinski D, van Zandbergen G, Laufs H, Hansen B, Muller K . Inhibition of the spontaneous apoptosis of neutrophil granulocytes by the intracellular parasite Leishmania major. J Immunol. 2002; 169(2):898-905. DOI: 10.4049/jimmunol.169.2.898. View

Cassatella M, Bazzoni F, Ceska M, Ferro I, Baggiolini M, Berton G . IL-8 production by human polymorphonuclear leukocytes. The chemoattractant formyl-methionyl-leucyl-phenylalanine induces the gene expression and release of IL-8 through a pertussis toxin-sensitive pathway. J Immunol. 1992; 148(10):3216-20. View

Laufs H, Muller K, Fleischer J, Reiling N, Jahnke N, Jensenius J . Intracellular survival of Leishmania major in neutrophil granulocytes after uptake in the absence of heat-labile serum factors. Infect Immun. 2002; 70(2):826-35. PMC: 127667. DOI: 10.1128/IAI.70.2.826-835.2002. View

van den Berg C, Aerts P, Van Dijk H . In vivo anti-complementary activities of the cobra venom factors from Naja naja and Naja haje. J Immunol Methods. 1991; 136(2):287-94. DOI: 10.1016/0022-1759(91)90015-8. View

Guy R, Belosevic M . Comparison of receptors required for entry of Leishmania major amastigotes into macrophages. Infect Immun. 1993; 61(4):1553-8. PMC: 281400. DOI: 10.1128/iai.61.4.1553-1558.1993. View

Joshi P, Sacks D, Modi G, McMaster W . Targeted gene deletion of Leishmania major genes encoding developmental stage-specific leishmanolysin (GP63). Mol Microbiol. 1998; 27(3):519-30. DOI: 10.1046/j.1365-2958.1998.00689.x. View

Pahl A, Kuhlbrandt U, Brune K, Rollinghoff M, Gessner A . Quantitative detection of Borrelia burgdorferi by real-time PCR. J Clin Microbiol. 1999; 37(6):1958-63. PMC: 84995. DOI: 10.1128/JCM.37.6.1958-1963.1999. View

Chaudhuri G, Chang K . Acid protease activity of a major surface membrane glycoprotein (gp63) from Leishmania mexicana promastigotes. Mol Biochem Parasitol. 1988; 27(1):43-52. DOI: 10.1016/0166-6851(88)90023-0. View

Muller K, van Zandbergen G, Hansen B, Laufs H, Jahnke N, Solbach W . Chemokines, natural killer cells and granulocytes in the early course of Leishmania major infection in mice. Med Microbiol Immunol. 2002; 190(1-2):73-6. DOI: 10.1007/s004300100084. View

10.

Dominguez M, Moreno I, Lopez-Trascasa M, Torano A . Complement interaction with trypanosomatid promastigotes in normal human serum. J Exp Med. 2002; 195(4):451-9. PMC: 2193616. DOI: 10.1084/jem.20011319. View

11.

Silva R, Hall B, Joiner K, Sacks D . CR1, the C3b receptor, mediates binding of infective Leishmania major metacyclic promastigotes to human macrophages. J Immunol. 1989; 143(2):617-22. View

12.

Brittingham A, Morrison C, McMaster W, McGwire B, Chang K, Mosser D . Role of the Leishmania surface protease gp63 in complement fixation, cell adhesion, and resistance to complement-mediated lysis. J Immunol. 1995; 155(6):3102-11. View

13.

Vogel C, MULLER-EBERHARD H . Cobra venom factor: improved method for purification and biochemical characterization. J Immunol Methods. 1984; 73(1):203-20. DOI: 10.1016/0022-1759(84)90045-0. View

14.

Chen L, Watanabe T, Watanabe H, Sendo F . Neutrophil depletion exacerbates experimental Chagas' disease in BALB/c, but protects C57BL/6 mice through modulating the Th1/Th2 dichotomy in different directions. Eur J Immunol. 2001; 31(1):265-75. DOI: 10.1002/1521-4141(200101)31:1<265::AID-IMMU265>3.0.CO;2-L. View

15.

Mosser D, Brittingham A . Leishmania, macrophages and complement: a tale of subversion and exploitation. Parasitology. 1997; 115 Suppl:S9-23. DOI: 10.1017/s0031182097001789. View

16.

Ember J, Sanderson S, Hugli T, MORGAN E . Induction of interleukin-8 synthesis from monocytes by human C5a anaphylatoxin. Am J Pathol. 1994; 144(2):393-403. PMC: 1887151. View

17.

Russell D, Wright S . Complement receptor type 3 (CR3) binds to an Arg-Gly-Asp-containing region of the major surface glycoprotein, gp63, of Leishmania promastigotes. J Exp Med. 1988; 168(1):279-92. PMC: 2188978. DOI: 10.1084/jem.168.1.279. View

18.

Beil W, Neugebauer D, Sorg C . Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice. J Leukoc Biol. 1992; 52(2):135-42. DOI: 10.1002/jlb.52.2.135. View

19.

Joshi P, Kelly B, Kamhawi S, Sacks D, McMaster W . Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor. Mol Biochem Parasitol. 2002; 120(1):33-40. DOI: 10.1016/s0166-6851(01)00432-7. View

20.

Mosser D, Edelson P . The third component of complement (C3) is responsible for the intracellular survival of Leishmania major. Nature. 1987; 327(6120):329-31. DOI: 10.1038/327329b0. View