Naslov
SGLT1 Deficiency Turns Listeria Infection into a Lethal Disease in Mice

Autori
Sharma, Piyush ; Khairnar, Vishal ; Vrhovac Madunić, Ivana ; Singh, Yogesh ; Pandyra, Aleksandra ; Salker, Madhuri S. ; Koepsell, Hermann ; Sabolić, Ivan ; Lang, Florian ; Lang, Philipp A ; Lang, Karl S.

Izvornik
Cellular physiology and biochemistry (1015-8987) 42 (2017), 4; 1358-1365

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Glucose uptake ; Na+-coupled glucose transport ; Listeria infection ; TNF-α and IL-12a ; Survival ; Liver ; Spleen ; Kidney ; Lung ; Bacterial clearance

Sažetak
Cellular glucose uptake may involve either non-concentrative glucose carriers of the GLUT family or Na+-coupled glucose-carrier SGLT1, which accumulates glucose against glucose gradients and may thus accomplish cellular glucose uptake even at dramatically decreased extracellular glucose concentrations. SGLT1 is not only expressed in epithelia but as well in tumour cells and immune cells. Immune cell functions strongly depend on their metabolism, therefore we hypothesized that deficiency of SGLT1 modulates the defence against bacterial infection. To test this hypothesis, we infected wild type mice and gene targeted mice lacking functional SGLT1 with Listeria monocytogenes. SGLT1 deficient mice and wild type littermates were infected with 1x104 CFU Listeria monocytogenes intravenously. Bacterial titers were determined by colony forming assay, SGLT1, TNF-α, IL-6 and IL-12a transcript levels were determined by qRTPCR, as well as SGLT1 protein abundance and localization by immunohistochemistry. Genetic knockout of SGLT1 (Slc5a1–/– mice) significantly compromised bacterial clearance following Listeria monocytogenes infection with significantly enhanced bacterial load in liver, spleen, kidney and lung, and significantly augmented hepatic expression of TNF-α and IL- 12a. While all wild type mice survived, all SGLT1 deficient mice died from the infection. SGLT1 is required for bacterial clearance and host survival following murine Listeria infection.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA