Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice.
Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice.
复制标题
遗传背景影响小鼠皮肤墨西哥乳杆菌感染的免疫反应和疾病结果。
DOI：
10.1093/intimm/dxh313
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发表时间：
2005
影响因子：
4.4
通讯作者：
Satoskar,AbhayR
中科院分区：
文献类型：
--
作者：
Rosas,LuciaE;Keiser,Tracy;Barbi,Joseph;Satoskar,AnjaliA;Septer,Alecia;Kaczmarek,Jennifer;Lezama-Davila,ClaudioM;Satoskar,AbhayR
The experimental model of high-doseLeishmania mexicanainfection is used frequently to study molecular mechanisms regulating Th2 response since most inbred mice regardless of their genetic background display Th2 cytokine-dependent susceptibility toL. mexicanaunlikeLeishmania major. Here, we analyzed the course ofL. mexicanainfection in BALB/c, C57BL/6 and CBA/J mouse strains using low-dose ear infection model that mimics natural transmission. Although all three strains were equally susceptible to high-dose back rumpL. mexicanainfection, they displayed marked differences in their ability to control parasite growth after low-dose ear infection.Leishmania mexicana-infected BALB/c mice produced high levels of Th2-associated cytokines and developed non-healing lesions full of parasites, whereas CBA/J mice preferentially produced Th1-associated IFN-γ but low levels of IL-4, and developed small self-resolving lesions. Both BALB/c and C57BL/6 mice produced comparable amounts of IFN-γ followingL. mexicanainfection, but later produced less Th2-associated cytokines, and exhibited an ‘intermediate’ susceptibility phenotype characterized by lesion sizes that were significantly smaller than BALB/c mice but larger than CBA/J mice. Interestingly, all three strains also showed marked differences in trafficking of macrophages, CD4+ T cells and CD8+ T cells into their lesions. Finally, we analyzed the course of low-doseL. mexicanainfection in signal transducers and activators of transcription (STAT) 6−/− and STAT6+/+ BALB/c mice. We found that STAT6−/− mice mount a Th1 response, produce high levels of IL-12 and IFN-γ and develop smaller lesions containing fewer parasites as compared with STAT6+/+ mice. Our findings demonstrate that genetic background plays a critical role in determining susceptibility of inbred mice to low-doseL. mexicanainfection. Furthermore, together with our previous findings, they show that STAT6-mediated signaling is involved in mediating susceptibility toL. mexicanafollowing both high-dose back rump and low-dose ear dermis infection.
