Freitas Jorge M, Andrade Luciana O, Pires Simone F, Lima Ricardo, Chiari Egler, Santos Ricardo R, Soares Milena, Machado Carlos R, Franco Gloria R, Pena Sergio D J, Macedo Andrea M
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
PLoS One. 2009;4(4):e5113. doi: 10.1371/journal.pone.0005113. Epub 2009 Apr 1.
We have previously demonstrated that both parasite genetic variability and host genetic background were important in determining the differential tissue distribution of the Col1.7G2 and JG T. cruzi monoclonal strains after artificial infections in mice. We observed that the JG strain was most prevalent in hearts of mouse lineages with the MHC haplotype H-2(d) (BALB/c and DBA2), while Col1.7G2 was predominant in hearts from C57BL/6 mice, which have the H-2(b) haplotype. To assess whether the MHC gene region indeed influenced tissue tropism of T. cruzi, we used the same two parasite strains to infect C57BL/6 (H-2(b)) and C57BLKS/J (H-2(d)) mice; the latter strain results from the introgression of DBA2 MHC region into the C57BL/6 background. We also performed ex vivo infections of cardiac explants from four congenic mice lineages with the H-2(b) and H-2(d) haplotypes arranged in two different genetic backgrounds: C57BLKS/J (H-2(d)) versus C57BL/6 (H-2(b)) and BALB/c (H-2(d)) versus BALB/B10-H2(b) (H-2(b)). In agreement with our former observations, Col1.7G2 was predominant in hearts from C57BL/6 mice (H-2(b)), but we observed a clear predominance of the JG strain in hearts from C57BLKS/J animals (H-2(d)). In the ex vivo experiments Col1.7G2 also prevailed in explants from H-2(b) animals while no predominance of any of the strains was observed in H-2(d) mice explants, regardless of the genetic background. These observations clearly demonstrate that the MHC region influences the differential tissue distribution pattern of infecting T. cruzi strains, which by its turn may be in a human infection the determinant for the clinical forms of the Chagas disease.
我们之前已经证明，在小鼠人工感染后，寄生虫的遗传变异性和宿主的遗传背景对于决定克氏锥虫Col1.7G2和JG单克隆菌株的不同组织分布都很重要。我们观察到，JG菌株在具有MHC单倍型H-2(d)的小鼠品系（BALB/c和DBA2）的心脏中最为普遍，而Col1.7G2在具有H-2(b)单倍型的C57BL/6小鼠的心脏中占主导地位。为了评估MHC基因区域是否确实影响克氏锥虫的组织嗜性，我们使用相同的两种寄生虫菌株感染C57BL/6（H-2(b)）和C57BLKS/J（H-2(d)）小鼠；后一种菌株是通过将DBA2 MHC区域渗入C57BL/6背景中产生的。我们还对来自四个具有H-2(b)和H-2(d)单倍型的同源小鼠品系的心脏外植体进行了体外感染，这些品系排列在两种不同的遗传背景中：C57BLKS/J（H-2(d)）与C57BL/6（H-2(b)）以及BALB/c（H-2(d)）与BALB/B10-H2(b)（H-2(b)）。与我们之前的观察结果一致Col1.7G2在C57BL/6小鼠（H-2(b)）的心脏中占主导地位，但我们观察到JG菌株在C57BLKS/J动物（H-2(d)）的心脏中明显占主导地位。在体外实验中，Col1.7G2在H-2(b)动物的外植体中也占优势，而在H-2(d)小鼠外植体中未观察到任何菌株占主导地位，无论其遗传背景如何。这些观察结果清楚地表明，MHC区域影响感染克氏锥虫菌株的不同组织分布模式，而这反过来在人类感染中可能是恰加斯病临床形式的决定因素。
