Banus Sander, Vandebriel Rob J, Pennings Jeroen L A, Gremmer Eric R, Wester Piet W, van Kranen Henk J, Breit Timo M, Demant Peter, Mooi Frits R, Hoebee Barbara, Kimman Tjeerd G
Laboratory for Infectious Diseases and Screening, National Institute of Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands.
BMC Microbiol. 2007 Oct 12;7:88. doi: 10.1186/1471-2180-7-88.
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.
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).
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.
百日咳博德特氏菌感染的易感性差异很大。这些差异部分可由宿主遗传因素解释。HcB - 28小鼠比C3H小鼠对百日咳博德特氏菌感染更具抵抗力，这部分可归因于12号染色体上的百日咳博德特氏菌易感性位点1（Bps1）。该位点存在C57BL / 10基因组而非C3H基因组导致肺部细菌数量减少。为了进一步阐明宿主遗传因素，特别是Bps1位点在百日咳博德特氏菌感染中的作用，并鉴定该区域内的候选基因，我们比较了百日咳博德特氏菌接种后C3H和HcB - 28小鼠品系肺部的表达谱。这些小鼠基因组的12.5%来自不同的遗传背景。
接种百日咳博德特氏菌后，两种小鼠品系的肺部有2353个基因差异表达。两种小鼠品系之间有206个基因差异表达，但值得注意的是，这些基因在百日咳博德特氏菌感染后均未上调或下调。在这206个基因中，17个位于Bps1区域。其中8个基因在两种小鼠品系之间表现出强烈的基因表达差异，定位于免疫球蛋白重链复合体（Igh）。
尽管百日咳博德特氏菌感染过程存在差异，但两种小鼠品系在百日咳博德特氏菌感染后的基因表达变化高度相同。由于小鼠品系之间差异调节的基因仅在感染前表现出表达差异，因此这种基因调节的内在差异似乎可能参与了百日咳博德特氏菌感染易感性差异的决定。或者，这种易感性的遗传差异可能由这两种小鼠品系之间未差异调节的基因解释。Igh复合体中的基因，其中包括Igh - 1a / b，可能是解释百日咳博德特氏菌易感性差异的候选基因。因此，通过微阵列分析，我们显著减少了Bps1位点内候选易感性基因的数量。进一步的工作应确定Igh复合体在百日咳博德特氏菌感染中的作用。
