Comparative gene expression profiling in two congenic mouse strains following Bordetella pertussis infection.
BACKGROUND
Susceptibility to Bordetella pertussis infection varies widely. These differences can partly be explained by genetic host factors. HcB-28 mice are more resistant to B. pertussis infection than C3H mice, which could partially be ascribed to the B. pertussis susceptibility locus-1 (Bps1) on chromosome 12. The presence of C57BL/10 genome on this locus instead of C3H genome resulted in a decreased number of bacteria in the lung. To further elucidate the role of host genetic factors, in particular in the Bps1 locus, in B. pertussis infection, and to identify candidate genes within in this region, we compared expression profiles in the lungs of the C3H and HcB-28 mouse strains following B. pertussis inoculation. Twelve and a half percent of the genomes of these mice are from a different genetic background.


RESULTS
Upon B. pertussis inoculation 2,353 genes were differentially expressed in the lungs of both mouse strains. Two hundred and six genes were differentially expressed between the two mouse strains, but, remarkably, none of these were up- or down-regulated upon B. pertussis infection. Of these 206 genes, 17 were located in the Bps1 region. Eight of these genes, which showed a strong difference in gene expression between the two mouse strains, map to the immunoglobulin heavy chain complex (Igh).


CONCLUSIONS
Gene expression changes upon B. pertussis infection are highly identical between the two mouse strains despite the differences in the course of B. pertussis infection. Because the genes that were differentially regulated between the mouse strains only showed differences in expression before infection, it appears likely that such intrinsic differences in gene regulation are involved in determining differences in susceptibility to B. pertussis infection. Alternatively, such genetic differences in susceptibility may be explained by genes that are not differentially regulated between these two mouse strains. Genes in the Igh complex, among which Igh-1a/b, are likely candidates to explain differences in susceptibility to B. pertussis. Thus, by microarray analysis we significantly reduced the number of candidate susceptibility genes within the Bps1 locus. Further work should establish the role of the Igh complex in B. pertussis infection.
Banus
Sander
S
Laboratory for Infectious Diseases and Screening, National Institute of Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands. Sander.Banus@RIVM.NL
Vandebriel
Rob J
RJ
Pennings
Jeroen L A
JL
Gremmer
Eric R
ER
Wester
Piet W
PW
van Kranen
Henk J
HJ
Breit
Timo M
TM
Demant
Peter
P
Mooi
Frits R
FR
Hoebee
Barbara
B
Kimman
Tjeerd G
TG
D000818:Animals; D001886:Bordetella pertussis / Q000472:pathogenicity*; D004198:Disease Susceptibility; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain; D015431:Weight Loss; D014917:Whooping Cough / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
D007143:Immunoglobulin Heavy Chains; D011506:Proteins