Trypanosoma congolense: Paraoxonase 1 prolongs survival of infected mice

• Published in: Experimental parasitology 2006-11, Vol.114 (3), p.240-245
• Main Authors: Bhasin, Kum Kum, Yu, Janet M., Tward, Aaron, Shih, Diana, Campbell, David A., Lusis, Aldons J.
• Format: Article
• Language: English
• Subjects: Animals; ApoA-II; apolipoprotein A-II; Apolipoprotein A-II - immunology; Aryldialkylphosphatase - genetics; Aryldialkylphosphatase - immunology; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; HDL; high density lipoprotein; Humans; Life cycle. Host-agent relationship. Pathogenesis; Lipoproteins, HDL - chemistry; Lipoproteins, HDL - immunology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; paraoxonase; PON; Protozoa; TLF; Trypanosoma; Trypanosoma brucei brucei - immunology; Trypanosoma congolense; Trypanosoma congolense - immunology; trypanosome lytic factor; Trypanosomiasis, African - immunology
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2006.03.010

In vitro studies have suggested that a fraction of human high density lipoprotein (HDL), termed trypanosome lysis factor (TLF), can protect against trypanosome infection. We examined the involvement of two proteins located in the TLF fraction, apolipoprotein A-II (apoA-II) and paraoxonase 1 (PON1), against trypanosome infection. To test whether PON1 is involved in trypanosome resistance, we infected human PON1 transgenic mice, PON1 knockout mice, and wild-type mice with Trypanosoma congolense. When challenged with the same dosage of trypanosomes, mice overexpressing PON1 lived significantly longer than wild-type mice, and mice deficient in PON1 lived significantly shorter. In contrast, mice overexpressing another HDL associated protein, apoA-II, had the same survival as wild-type mice. Together, these data suggest that PON1 provides protection against trypanosome infection. In vitro studies using T. brucei brucei indicated that HDL particles containing PON1 and those depleted of PON1 did not differ in their lysis ability, suggesting that protection by PON1 is indirect. Our data are consistent with an in vivo role of HDL protection against trypanosome infection.