The role of NK and ILC1 cells in the control of murine cytomegalovirus during ontogeny

Abstract

Ljudski citomegalovirus (HCMV) je jedan od najrasprostranjenijih virusa diljem svijeta. Njegova raširenost predstavlja veliki problem u zdravstvenom sektoru zbog toga što može nakon infekcije ostaviti ozbiljne posljedice, pogotovo ukoliko dođe do prijenosa virusa s trudnice na plod, čime uzrokuje prirođenu infekciju HCMV-om koja može imati i letalan ishod. Imunosni sustav u prenatalnom i ranom postnatalnom razdoblju nije razvijen kao u odraslih te je nedostatak zrelosti razlog tome što infekcije u tom periodu mogu uzrokovati ozbiljne posljedice. Mehanizmi kako nerazvijeni imunosni sustav, odnosno prirođena imunost, štiti plod i novorođenčad od infekcija različitim patogenima su slabo istraženi. Za potrebe istraživanja HCMV-a koristi se mišjicitomegalovirus (MCMV) s kojim dijeli mnoge sličnosti u temeljnoj biologiji i patogenezi, te zbog toga infekcija miševa MCMV-om predstavlja najčešće korišteni model infekcije citomegalovirusom. U ovom istraživanju koristili smo transgenične miševe, pristup uklanjanja imunoloških stanica monoklonskim protutijelima, te rekombinantni MCMV kako bi istražili ulogu stanica NK i ILC1 u nadzoru infekcije MCMV-om u novookoćenih miševa. Transgenične miševe smo genotipizirali PCR-om, prisustvo stanica NK i ILC1 odredili smo metodom protočne citometrije, dok smo testom virusnih čistina odredili količinu virusa u ispitivanim organima. Rezultati ovog rada pokazali su kako stanice urođene imunosti, stanice NK i ILC1, imaju važnu ulogu u nadzoru infekcije MCMV-om u jetri novookoćenih miševa. Daljnja istraživanja će pružiti bolje razumijevanje neonatalnog imunosnog sustava.Human cytomegalovirus (HCMV) is one of the most widespread viruses worldwide. It is a major problem in healthcare because the infecion can leaveserious consequences, especially if the virus is transmitted from the pregnant woman to the fetus, i.e., if it causes congenital HCMV infection that can havea fatal outcome. The immune system in the prenatal and early postnatal period is immature as compared to adults, and the immaturity is the reason why infections in that period can result in serious consequences. The mechanisms by which an underdeveloped immune system, i.e. innate immunity, protects the fetus and newborns from infections by various pathogens have been poorly investigated. To study HCMV, murine cytomegalovirus (MCMV) is often used, which shares many biological similarities and pathogenesis; therefore, infection of mice with MCMV is the most commonly used model of cytomegalovirus infection. In this study, we used transgenic mice, an immune cell depletion approach with monoclonal antibodies, and recombinant MCMV to investigate the role of NK cells and ILC1 cells in the control of MCMV infection in newborn mice. The transgenic mice were genotyped by PCR, the presence of NK and ILC1 cells was determinedby flow cytometry method, while the levels of virus in the examined organs was determined by the plaque assay. The results of this work showed that innate immune cells, NK cells and ILC1, play an important role in controlling MCMV infection in the liver of newborn mice. Further research will provide a better understanding of the neonatal immune system