The Expression And Significance Of SCARB2, TLRs And Related Signaling Molecules In Cases Infected With EV71

Objective: Enterovirus71(EV71) infection can cause severe hand, foot andmouth disease (HFMD)easily for infants and young children.According tostatistics, the number of EV71infection had risen to the first infectious disease in2010.The morbidity and mortality of EV71infection are still high in recentyears,but its specific pathogenesis has not been clarified currently.Researches atthe cellular level have proved that scavenger receptor class B member2(SCARB2)is not only the receptor of EV71,but also the endogenic ligand of toll likereceptors(TLRs).Some researchers think TLRs can recognize EV71,but it isunclear that whether the TLRs may mediate the mixed antagonism responsesyndrome(MARS) caused by EV71infection.Studies about the relationship ofEV71infection and TLRs at human tissue level are not seen at present,therefore,this subject research analyses clinical data and pathological features of casesinfected with EV71, detects expressions of SCARB2, TLR3,TLR4,TLR7,TLR8,heat stress protein(HSP)60and high mobility group box-1protein (HMGB1)whichare endogenic ligands of TLRs, myeloid differentiation primary response protein 88(MyD88)which is signaling molecule of TLRs,to study the significance of thesefactors in EV71infection and provide new ideas of diagnosis and treatment forHFMD.Methods:The lung, brain and spinal cord tissues and clinical data of9casesinfected with EV71(EV71group) were selected as research objects,7cases diedof accidents were selected as control.Families of all cases had signed the informedconsents,and this topic had been agreed by the hospital ethics committee.Clinicaldata after EV71infection was analyzed,the pathological features were observed byhematoxylin and eosin(HE) staining, and expressions of SCARB2,TLRs,HSP60,HMGB1,MyD88were tested by immunohistochemistry(IHC), positive integratedoptical density(IOD) was detected by using picture analysis software,all theexperimental data was analyzed by SPSS17.0statistical software.Results:(1) All nine cases had fever,vomiting,startle response,shake,fatigueand pulmonary edema in chest X-ray.(2)HE staining:Congestion, extensiveedema and inflammatory cells infiltration in alveolar walls were found inlungs,transparent membrane was seen obviously in alveolar lumen from1case;Brain and spinal cord tissues appeared perivascular cuffing of lymphocytes,degeneration and necrosis of nerve cells, cribriform softens,satellitism andneuronophagia,glial nodule.(3)IHC results:①SCARB2in EV71group and thecontrol were both positive in lung, brain tissues.The lung and brain IOD values ofEV71group were415182.82,284651.83, which were higher than the controlgroup lung and brain5105.04and12945.27,(P<0.01);The positive expression IODof SCARB2in brain, brainstem and spinal cord in EV71group were224432.81,365210.34,394851.72,respectively,the differences between brain and brainstem, between brain and spinal cord were both statistically significant (P <0.01), but there was no statistically significant difference between brainstem andspinal cord (P>0.05);②All the TLR(3,4,7,8)were positive expressed in the lungand brain tissues of both EV71group and the control group. The IOD of TLR(3,4,7,8)in lung of EV71group were85676.87,90362.70,191180.48,179467.14, incontrol group were16251.47,20870.81,21897.83,19460.94,differences betweentwo groups were both statistically significant (P<0.05);The IOD of TLR(3,4,7,8)in brain of EV71group were73805.62,28187.45,75492.00,68677.57,in controlgroup were62380.04,5387.36,21207.79,20583.46,the expression differences ofTLR(4,7,8) between two groups were both statistically significant (P<0.05),butthere was no statistically difference of TLR3IOD between two groups(P>0.05).③H SP60was expressed strong positively in lung tissue of EV71group, the IODwas410950.24, the control group showed weakly positive to positive,IOD was11533.41,P<0.05;brain tissue of EV71group showed positive reaction,the IODwas195227.91, whereas the control brain tissue were negative expression and onlypartial nerve cells in just1case of brainstem showed weak positive signals,P<0.05.④HMGB1expressed positively only in part of inflammation cells in lung tissuefrom just1case in EV71group,2cases in control group,partial nerve cells in just1case of brain showed weak positive signals in control group,the rest of lung andbrain were negative expression,there was no statistically difference between twogroups.⑤M yD88was positively expressed in lung tissue in two groups,the IODvalues were63055.50,16571.72, P<0.05;Scattered mononuclear macrophage cells were positive in brain from only2cases of EV71group,but brain in control didnot see positive expression,P>0.05.Conclusions: The patients mainly died of severe encephalitis, brainstemencephalitis and neurogenic pulmonary edema after EV71infection. The severityand neurotropism of EV71infection may be associated with the high expression ofSCARB2.TLRs,HSP60and MyD88may form a complexity inflammatoryregulation network that participate in the development of HFMD;WhetherHMGB1has potential correlation with EV71infection remains to be furtherstudied.