Host lung immunity is severely compromised during tropical pulmonary eosinophilia: role of lung eosinophils and macrophages

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: filariasis;    flow cytometry;    gene expression;    alternative activation;    proapoptotic genes;   

DOI  :  10.1189/jlb.4A0715-309RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Eosinophilsplayacentralroleinthepathogenesisoftropicalpulmonaryeosinophilia,arare,butfatal,manifestationoffilariasis.However,noexhaustivestudyhasbeendonetoidentifythegenesandproteinsofeosinophilsinvolvedinthepathogenesisoftropicalpulmonaryeosinophilia.Inthepresentstudy,weestablishedamousemodeloftropicalpulmonaryeosinophiliathatmimickedfilarialmanifestationsofhumantropicalpulmonaryeosinophiliapathogenesisandusedflowcytometry‐assistedcellsortingandreal‐timeRT‐PCRtostudythegeneexpressionprofileofflow‐sorted,lungeosinophilsandlungmacrophagesduringtropicalpulmonaryeosinophiliapathogenesis.OurresultsshowthattropicalpulmonaryeosinophiliamiceexhibitedincreasedlevelsofIL‐4,IL‐5,CCL5,andCCL11inthebronchoalveolarlavagefluidandlungparenchymaalongwithelevatedtitersofIgEandIgGsubtypesintheserum.Alveolarmacrophagesfromtropicalpulmonaryeosinophiliamicedisplayeddecreasedphagocytosis,attenuatednitricoxideproduction,andreducedT‐cellproliferationcapacity,andFACS‐sortedlungeosinophilsfromtropicalpulmonaryeosinophiliamiceupregulatedtranscriptlevelsofficolinAandanti‐apoptoticgeneBcl2,butproapoptoticgenesBimandBaxweredownregulated.Similarly,flow‐sortedlungmacrophagesupregulatedtranscriptlevelsofTLR‐2,TLR‐6,arginase‐1,Ym‐1,andFIZZ‐1butdownregulatednitricoxidesynthase‐2levels,signifyingtheiralternativeactivation.Takentogether,weshowthatthepathogenesisoftropicalpulmonaryeosinophiliaismarkedbyfunctionalimpairmentofalveolarmacrophages,alternativeactivationoflungmacrophages,andupregulationofanti‐apoptoticgenesbyeosinophils.Theseeventscombinetogethertocauseseverelunginflammationandcompromisedlungimmunity.Therapeuticinterventionsthatcanboosthostimmuneresponseinthelungsmightthusproviderelieftopatientswithtropicalpulmonaryeosinophilia...

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