Apolipoprotein E-deficient mice develop an anti-Chlamydophila pneumoniae T helper 2 response and resist vascular infection.
BACKGROUND
Hypercholesterolemia could inhibit the immune response against various pathogens. No information is available about its impact on the immune response toward Chlamydophila pneumoniae.


METHODS
Apolipoprotein E (apoE)-deficient and wild-type mice fed a normal diet were infected with a single intranasal inoculation of viable C. pneumoniae.


RESULTS
Whereas interferon gamma concentrations (T helper 1 response) were similar in the lungs and spleen of apoE-deficient and wild-type mice, increased concentrations of interleukin 10, interleukin 6, and interleukin 4 (T helper 2 response) were found in the lungs of apoE-deficient mice. The spleen B lymphocyte percentage and interleukin 4 levels and serum specific antibody titers were higher in apoE-deficient mice. C. pneumoniae infection was facilitated neither in the lungs nor in the aorta of these mice. On the contrary, the number of apoE-deficient mice with detectable levels of bacterial DNA in the aorta was clearly decreased. When low-density lipoprotein receptor-deficient mice fed a normal diet were similarly infected, no difference in the interleukin 4 concentration and infection level was observed in the lungs and no protection was found in the aorta.


CONCLUSIONS
Mild hypercholesterolemia in mice does not facilitate C. pneumoniae persistence in the vascular wall. ApoE deficiency, rather than mild hypercholesterolemia, probably favors the development of an unusual anti-C. pneumoniae T helper 2 response and protects against vascular infection.
Nazzal
Dani
D
INSERM Unité 858, Institute of Molecular Medicine of Rangueil, Institut Fédératif de Recherche F150, and University Paul Sabatier, Toulouse Cedex 4, France.
Therville
Nicole
N
Yacoub-Youssef
Houda
H
Garcia
Virginie
V
Thomsen
Mogens
M
Levade
Thierry
T
Segui
Bruno
B
Benoist
Hervé
H
D000818:Animals; D001011:Aorta / Q000382:microbiology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D023521:Chlamydophila Infections / Q000276:immunology* / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology; D014652:Vascular Diseases / Q000276:immunology* / Q000382:microbiology
D001057:Apolipoproteins E; D016207:Cytokines