Matsumoto Takashi, Shiva Daisuke, Kawanishi Noriaki, Kato Yasuko, Woods Jeffrey A, Yano Hiromi
Microbiology, Department of Infectious Disease, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
Exerc Immunol Rev. 2008;14:38-50.
In general, systemic bacterial infections induce sickness behavior. In mice, lipopolysaccharide (LPS), a component of gram-negative bacteria, strongly reduces physical activity via toll-like receptor (TLR) 4. However, gram-negative bacteria, such as Salmonella, also express flagella containing flagellin (FG) which binds to TLR5 and induces pro-inflammatory cytokine production. It is unclear whether FG induces sickness behavior. To determine whether Salmonella administration regulates the reduction of voluntary physical activity in mice, male C3H/HeN (wild type) and C3H/HeJ (tlr4 gene mutated) mice were administered living Salmonella (live) and examined for wheel-running activity. The production of TNF-alpha in RAW 264 cells was measured by the ELISA assay under both live and heat-killed (HK) Salmonella conditions in vitro. Wheel-running activity in both C3H/HeJ and C3H/HeN mice after i.p. injection of live Salmonella (1 x 10(6) CFU/kg) was significantly lower than that in vehicle groups (p < 0.01, respectively), although wheel-running activity in C3H/HeJ mice was not reduced after i.p. injection of HK Salmonella (1 x 10(6) CFU/kg). Furthermore, TNF-alpha production from RAW 264 cells with HK Salmonella treatment at the early phase was higher than that with live Salmonella treatment. Interestingly, gentamicin-treated (GMT) Salmonella, (which have bacterial flagella removed), did not induce reduction of wheel-running activity, although injection of the flagella-rich supernatant of GMT Salmonella significantly reduced it (p < 0.01). Indeed, FG treatment also induced reduction of wheel-running activity in mice (p < 0.01). Our findings suggest that the Salmonella-induced reduction of voluntary physical activity might be regulated by FG via TLR5, but not LPS via TLR4 in mice.
一般来说，全身性细菌感染会引发疾病行为。在小鼠中，革兰氏阴性菌的一种成分脂多糖（LPS）通过Toll样受体（TLR）4强烈降低身体活动。然而，革兰氏阴性菌，如沙门氏菌，也表达含有鞭毛蛋白（FG）的鞭毛，鞭毛蛋白与TLR5结合并诱导促炎细胞因子产生。目前尚不清楚FG是否会引发疾病行为。为了确定给予沙门氏菌是否会调节小鼠自主身体活动的减少，对雄性C3H/HeN（野生型）和C3H/HeJ（tlr4基因突变型）小鼠给予活的沙门氏菌（活菌），并检测其轮转活动。在体外活的和热灭活（HK）的沙门氏菌条件下，通过ELISA测定法测量RAW 264细胞中TNF-α的产生。腹腔注射活的沙门氏菌（1×10⁶CFU/kg）后，C3H/HeJ和C3H/HeN小鼠的轮转活动均显著低于载体组（分别为p < 0.01），尽管腹腔注射HK沙门氏菌（1×10⁶CFU/kg）后C3H/HeJ小鼠的轮转活动并未降低。此外，早期用HK沙门氏菌处理的RAW 264细胞中TNF-α的产生高于用活的沙门氏菌处理的细胞。有趣的是，用庆大霉素处理（GMT）的沙门氏菌（去除了细菌鞭毛）并未诱导轮转活动减少，尽管注射GMT沙门氏菌富含鞭毛的上清液可显著降低轮转活动（p < 0.01）。事实上，FG处理也会诱导小鼠轮转活动减少（p < 0.01）。我们的研究结果表明，沙门氏菌诱导的自主身体活动减少可能是由FG通过TLR5调节的，而不是由LPS通过TLR4在小鼠中调节的。
