Chapter 10 : Immune Recognition and Host Cell Response during Infection

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Innate immune cells possess multiple germ line-encoded receptors that have evolved to broadly distinguish between self and nonself. These receptors are called pathogen recognition receptors (PRRs), and they detect conserved structures called microbe-associated molecular patterns (MAMPs) that are present on microbes. Although there is a finite number of PRRs, they are used in various combinations to recognize different intracellular pathogens, and even different species of . infection leads to expression of beta interferon (IFN-β) and interleukin-10 (IL-10) in infected cells. This chapter reviews the various PRRs that recognize chlamydiae and the ensuing cellular signaling pathways that result in cytokine induction. Initially, there is recognition at the surface of the host cell, but the majority of recognition occurs intracellularly. The Toll-like receptors (TLRs) are responsible for the recognition of unique MAMPs, such as bacterial lipoprotein, which initiate an immediate cytokine response upon infection. The evolution of inflammatory pathway appears to be driven by viruses as the host cell incorporates multiple means of inducing IFN-β to limit viral replication. A number of studies described in the chapter used human or mouse cell lines or mouse macrophages but not primary cervical epithelial cells. Although cell lines and mouse macrophages provide clues about the specific use of receptors and signaling pathways, the results have to be confirmed with the cells that are infected in the natural host. Additional DNA sensors need to be discovered in the coming years and more will be learned about cell type-specific use of the TLRs.

Citation: Nagarajan U. 2012. Immune Recognition and Host Cell Response during Infection, p 217-239. In Tan M, Bavoil P (ed), Intracellular Pathogens I: . ASM Press, Washington, DC. doi: 10.1128/9781555817329.ch10

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Image of FIGURE 1

Schematic representation of the recognition of chlamydiae by TLR and NOD signaling pathways. TLR2 is the major TLR implicated in chlamydial recognition. TLR2 is normally expressed on the cell surface, but it has also been shown to localize in the vicinity of the chlamydial inclusion membrane. The specific chlamydial ligand recognized by TLR2 is not yet known. TLR4-mediated chlamydial recognition has been observed in the absence of TLR2 expression, and chlamydial Hsp60 is recognized as a TLR4 ligand. MyD88 is the common adaptor molecule for most TLRs and is necessary for TLR2/4-mediated activation of NF-κB and MAPK. This activation leads to expression of proinflammatory cytokine genes, which have been implicated in oviduct pathology during chlamydial genital infection. NOD1, an intracellular cytosolic receptor, also contributes to NF-κB activation by recognizing chlamydial peptidoglycan precursors. doi:10.1128/9781555817329.ch10.f1

Citation: Nagarajan U. 2012. Immune Recognition and Host Cell Response during Infection, p 217-239. In Tan M, Bavoil P (ed), Intracellular Pathogens I: . ASM Press, Washington, DC. doi: 10.1128/9781555817329.ch10
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Image of FIGURE 2

Schematic representation of inflammasome activation and caspase-1 activation during chlamydial infection. Cleavage of procaspase-1 to form active caspase-1 requires formation of the inflammasome. The inflammasome is a complex resulting from recognition of PRR or a danger signal by the NLRP proteins, the adaptor ASC and the procaspase-1. ASC is essential for the interaction of the pyrin (PYD) domain of NLRP with the CARD domain of procaspase-1. Of the NLRPs, NLRP3 recognizes ligands such as pore-forming toxins and danger signals like ATP, uric acid, or mitochondrial damage. NLRC4 recognizes the T3S apparatus and flagellin, AIM2 recognizes dsDNA, and NALP1b recognizes toxins such as Bacillus anthracis lethal toxin. During chlamydial infection, NLRP3 is involved in caspase-1 activation, but multiple NLRPs that are yet to be identified are likely activated. The chlamydial T3S apparatus contributes to caspase-1 activation, but the specific effectors and NLRP involved are not known. NLRC4 is not activated during chlamydial infection. doi:10.1128/9781555817329.ch10.f2

Citation: Nagarajan U. 2012. Immune Recognition and Host Cell Response during Infection, p 217-239. In Tan M, Bavoil P (ed), Intracellular Pathogens I: . ASM Press, Washington, DC. doi: 10.1128/9781555817329.ch10
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Image of FIGURE 3

Schematic representation of receptors engaged in IFN-β induction during chlamydial infection and the resulting signaling pathway. The adaptor molecule STING is involved in chlamydially induced IFN-β induction. DNA and RNA sensors DAI, IFI16, and RLRs, which function upstream of STING, do not contribute to IFN-β induction, but detection of chlamydial dicyclic nucleotide(s) has been implicated. STING activation leads to phosphorylation of IRF3 by the kinases TBK/IKKϵ. Phosphorylated IRF3 translocates to the nucleus, binds the IFN-β promoter, and initiates transcription cooperatively with p65 binding. NOD1 detection and signaling lead to NF-κB activation, which contributes to IFN-β induction. TLR3- and TRIF-mediated signaling has also been shown to contribute to IFN-β induction in mouse oviduct epithelial cells (dashed line/arrow).doi:10.1128/9781555817329.ch10.f3

Citation: Nagarajan U. 2012. Immune Recognition and Host Cell Response during Infection, p 217-239. In Tan M, Bavoil P (ed), Intracellular Pathogens I: . ASM Press, Washington, DC. doi: 10.1128/9781555817329.ch10
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