Abstract
Staphylococcus aureus (S. aureus) is a dangerous pathogen as well as a frequent colonizer, threatening human health worldwide. Protection against S. aureus infection is challenging, as the bacteria have sophisticated strategies to escape the host immune response. To maintain equilibrium with S. aureus, both innate and adaptive immune effector mechanisms are required. Dendritic cells (DCs) are critical players at the interface between the two arms of the immune system, indispensable for inducing specific T cell responses. In this review, we highlight the importance of DCs in mounting innate as well as adaptive immune responses against S. aureus with emphasis on their role in S. aureus-induced respiratory diseases. We also review what is known about mechanisms that S. aureus has adopted to evade DCs or manipulate these cells to its advantage.
Highlights
Staphylococcus aureus (S. aureus) can act as a commensal bacterium in humans, where it frequently colonizes the airways, skin and gut
We review different aspects of dendritic cells (DCs) physiology and how these cells interact with S. aureus during colonization and infection
We conclude that many microbial proteins have adjuvant activity, determining the cytokine and antibody profiles of the specific T and B cells. As this is an emerging topic, there are many open questions: How are DCs involved in the process? Are the superantigenic or enzymatic activities of the staphylococcal factors important for their allergenic properties? Are there general features of bacterial allergens? How does intrinsic adjuvanticity of bacterial antigens affect the outcome of vaccination, especially, if non-adjuvanted bacterial factors are used as vaccines? Is S. aureus able to initiate the allergic march in susceptible individuals, or does it merely exacerbate pre-existing allergic inflammation? We hypothesize that S. aureus allergens may sensitize vulnerable persons whose allergic reaction is potentiated by bacterial toxins and the pathogen-associated molecular patterns (PAMPs) in the airways
Summary
Staphylococcus aureus (S. aureus) can act as a commensal bacterium in humans, where it frequently colonizes the airways, skin and gut. To control the bacteria and the infected cells, the host immune system uses every level of its defense mechanisms [1]. The humoral arm of the innate immune system, the complement cascade, is indispensable in the defense against S. aureus Complement factors or their fragments can promote opsonization to facilitate microbial clearance (C3b) and drive inflammation (C3a and C5a). By inhibiting the central hub of the complement cascade, the C3 convertase, S. aureus reduces the production of C3b, C3a and C5a, interfering with both opsonization and inflammation [1,9] These findings are in line with the previously observed role of C3 in controlling S. aureus bacteremia [10]. It was shown that HIES patients have very low anti-S. aureus antibody titers, total serum IgG levels are in the normal range This is due to their impaired T cell response, which we discuss in detail below. Apenptit-imdeisc;roAbuiarl: Apeupretiodleyss;inA; BuCr:R:ABurceeolllyrseicne;ptBoCr;RD: CBs: cDelelndrericteicptcoerl;ls;DCC3s:: CDoemnpdlreitmicenctefllasc;toCr 33:; CColfm: Cplleummepnitngfafcatcotror3;; CColaf:: CClouamgupliansge;faCcRto1r:; CCooma:plCeomaegnutlarseec;epCtRor1:1;CEofmb:pElexmtreanctelrlueclaerptfiobrri1n;oEgfebn: Ebxintrdaicneglluplraorteifnib; rHinloag: eAnlpbhian-dhienmgolpyrsointe;iHn;lgH: Glaa: mAmlpah-hae-hmeomlyoslyinsi;nF;c:HFlrga:gmGeanmtmcray-shteamlliozlaybslien;; FFncb:: FFribagrimnoennet cctriyns-btailnlidzianbglep; rFontbei:nF;ibKraint:onCeacttianla-bsien;dLinugk:prLoetueikno; cKidaitn: ;CMataHlaCs:e;MLaujko:r Lheiustkooccoimdipna; tMibHiliCty: Mcoamjoprlehxi;stOoactoAm: pOa-taicbeitlyitlytrcaonmsfperlaesxe; OAa; PtASM: O: -Pahceentyollt-rsaonlusfbelreamseoAdu; lPinS;MP:VPLh:ePnaonlt-osno-lVuballeenmtinoeduleluinc;oPciVdLin: P(PaVnLto)n; R-VOaSle: nRteinacetivleeuocxoycigdeinnsp(PeVciLes);; SRAOgSs:: SRuepaecrtainvteigoenxys;gSeond:sSpuepcieerso;xiSdAegdsi:smSuuptaesrea;nStOigKen: sS;urSfoadce: Sfaucptoerropxriodme dotisinmgurteassies;taSnOcKe:toSuorxfaidcaetfivacetokrillpinrogm; SoptiAng: Sr.easuisrteaunscpertooteoixnidAa;tiSvpelsk:ilSleinrign;eSppAro:teSa. saeu-rleikues proteins;AS;xS: pStlsa:phSeyrloinxeanptrhointe;aTsCe-Rli:kTe cperlol treicnesp;toSrx;:TSLtRap2h: yTolollx-alinktehirne;ceTpCtoRr:2T; vcWelbl : rveocnepWtoirl;leTbrLaRn2d: Tfaocltlo-lri-kbeinrdecinepgtporo2t;evinW; Ub:rev:oUnrWeaislele.brand factor-binding protein; Ure: Urease
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