TABLE 1.

Summary of mammalian factors associated with the host response to UPEC-mediated UTI

Category or factorKnown or proposed role during UTIReference(s)
Adherence prevention
    Apoptosis/exfoliationRemoval of bound and intracellular UPEC10, 60, 81, 166, 176, 177, 189
    GAGsDecreases uroepithelium affinity for and/or inhibits UPEC adherence factors120, 158, 196, 197, 199, 237
    THPBinds FimH, innate-adaptive signaling172, 190, 192, 193, 195, 225
Antimicrobial peptides
    α-DefensinDisrupt UPEC membranes234, 294
    β-DefensinDisrupt UPEC membranes, DC maturation28, 174, 277
    CathelicidinDisrupt UPEC membranes46
Extracellular matrix
    InvolucrinMaintenance of uroepithelium215
    SuprabasinMaintenance of uroepithelium215
Signaling and cellular function
    Adaptor proteins
        ARH, Dab2, NumbAlternative clathrin adaptors for UPEC internalization64
        AP-2Primary clathrin adaptor for UPEC internalization64
        MyD88Proinflammatory gene expression73
        TRIFProinflammatory gene expression73
        TRAMProinflammatory gene expression73
    Enzymes
        AC3Proinflammatory gene expression, UPEC internalization suppression243, 245
        Histone deacetylase 6UPEC internalization53
        Rho GTPases (Rac-1, Cdc42)Mobilize actin for UPEC internalization56, 161, 243
        LysozymeCleaves bacterial peptidoglycan215
        NOS enzymesProduction of bactericidal reactive oxygen radicals, modifies dynamin facilitating UPEC entry into host cells130, 132, 181, 205, 281
    Kinases
        Aurora A kinaseUPEC internalization53
        FAKUPEC internalization65
        PI3-KUPEC internalization162
        PKAProinflammatory gene expression, UPEC internalization suppression243, 245
        Src family kinasesUPEC internalization65, 162
        Tyrosine kinasesUPEC internalization162
    Membrane and cytoskeleton
        ActinUPEC internalization162
        α-actininUPEC internalization162
        BidApoptosis141
        CholesterolUPEC internalization64
        ClathrinUPEC internalization64
        Caveolin-1UPEC internalization56, 64, 133
        DynaminUPEC internalization64, 281
        Kinesin light chain-2 (kinesin-1 motor complex)UPEC internalization53
        MicrotubulesUPEC internalization53
        VinculinUPEC internalization162
    Receptors
        β1 and α3 integrinUPEC internalization65
        CD46Opsonized UPEC internalization157
        CD48UPEC internalization18, 139
        CD55Regulator of the complement system, UPEC internalization133, 215
        CrryOpsonized UPEC internalization247
        GM-1 gangliosideUPEC internalization133
        ICAM-1 and β2 integrinRequired for efficient neutrophil migration to the infected urinary tract3, 227
        TLR4Recognition of UPEC by LPS and/or fimbriae in the bladder and kidney12, 14, 72, 79, 104-106, 175, 228, 229
        TLR5Recognition of UPEC flagellin in the bladder7
        TLR11Recognition of UPEC in the kidney296
        Uroplakin IIIaApoptosis/exfoliation258, 259
    Signaling molecules
        CalciumApoptosis/exfoliation, proinflammatory gene expression, UPEC internalization64, 245, 259
        cAMPIntracellular UPEC vesicle dynamics, mobilize actin for UPEC internalization, proinflammatory gene expression29, 243, 245
    Transcription factors
        CREBProinflammatory gene activation245
        NF-κBApoptosis, proinflammatory gene activation73, 142, 245
Iron homeostasis
    LactoferrinIron sequestration, disruption of Gram- negative bacterial membranes2, 49, 61, 90, 279
    Lcn2Bind and sequester enterobactin and enterobactin-like siderophores70, 74, 88, 110, 215
    TransferrinBind and transport iron, disruption of Gram- negative bacterial membranes61, 213, 279
Cytokines, chemokines, and complement
    CCL2, CCL4, CCL5, CXCL1Migration of T cells, monocytes, macrophages, NK cells, DCs, neutrophils121, 122
    G-CSFNeutrophil development and differentiation121, 122
    IL-6Acute phase response, B and T cell activation103, 104, 121, 122
    IL-8Neutrophil migration3, 4, 99, 102, 169, 229, 287
    IL-17Induce cytokine production important for phagocytic cell migrationSivick et al., submitted
    IL-1β, IL-12p40, TNF-αFever; T cell, NK, macrophage, and endothelial activation; Th1 response, local inflammation121, 122
    C3, factor BComplement factors upregulated in response to infection, C3 utilized for UPEC internalization215, 247
Phagocytic cells
    Dendritic cellsBacterial phagocytosis and killing, antigen presentation, IgA secretion62, 109, 144, 227, 255
    MacrophagesBacterial phagocytosis and killing, antigen presentation63, 109, 121
    NeutrophilsBacterial phagocytosis and killing4, 100, 236
Innate-like lymphocytes
    B-1 cellsSecrete IgM23, 115
    NKT cellsRapidly secrete cytokines, mediate UPEC clearance168, 182
    γδ T cellsRapidly secrete cytokine, including IL-1717, 40, 45, 115, 130, 163; Sivick, et al., submitted
Adaptive cellsa
    B cellsSecrete antibody109
    Th1 cellsProvide B cell help for an appropriate humoral response87, 130
    Th2 cellsUnknownNA
    Th17 cellsMay be dispensable for natural adaptive immune protective responsesSivick, et al., submitted
    Treg cellsUnknownNA
Antibodya
    IgANeutralization, opsonization, complement activation58, 116, 122, 217, 249, 263, 264
    IgGNeutralization, opsonization, complement activation58, 116, 122, 217, 249, 263, 264
    IgMMainly complement activation58, 116, 122, 217, 249, 263, 264
  • a In addition to the references cited, Table 2 provides data on humoral and cellular responses to vaccine candidates.