The human apoptosis inhibitor NAIP induces pyroptosis in macrophages infected with Legionella pneumophila

Katagiri, Nanako; Shobuike, Takeo; Chang, Bin; Kukita, Akiko; Miyamoto, Hiroshi

doi:10.1016/j.micinf.2012.03.006

Cited by 31 publications

(30 citation statements)

References 39 publications

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“…In accordance with other reports, 18,24,25) our study indicated that macrophage-like cell lines were appropriate and robust host cell lines used as infection models. Some studies have indicated many mouse lines including C57BL/6 and BALB/c are resistant to Legionella because whose allele of NAIP5 harbors a number of polymorphisms.…”

Section: Discussionsupporting

confidence: 92%

“…26,27) However, our results were in line with Barysheva et al and Katagiri et al showed that the total number of bacteria increased over time in murine J774.1A and Raw264.7 cells. 25,28) The reasons for the deviation are not very clear now. Among the non-phagocytic cell lines, MCF-7 and Beas-2B cells were better hosts for up to 24 h post-infection, whereas 16HBE was a proper host between 48 and 72 h post-infection.…”

Section: Discussionmentioning

confidence: 99%

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Intracellular Growth and Morphological Characteristics of <i>Legionella pneumophila</i> during Invasion and Proliferation in Different Cells

Xiong

Yamasaki

Chen

et al. 2017

Biological & Pharmaceutical Bulletin

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Various studies have been made to attempt to study the interaction between Legionella pneumophila and the host cells. In this research, we successfully constructed a L. pneumophila mutant strain that stably expressed high levels of green fluorescent protein and used this strain to evaluate the adherence, invasion and proliferation of L. pneumophila in association with several cell lines, including seven cell lines [human macrophage-like cell lines (U937, THP-1), murine macrophage-like cell lines (J774.1A, Raw264.7), human bronchial epithelial cell lines (16HBE, Beas-2B) and human cerrical cancer cell line (HeLa)] which have been used as the host models of L. pneumophila, and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Our results showed that the two newly tested cell lines are able to support the intracellular proliferation of L. pneumophila, and there were some morphological variations during the invasion and intracellular replication of L. pneumophila in different cell lines. These results can help us find out the common and special patterns of invasion and proliferation of L. pneumophila within different hosts. This is conducive to our knowledge on the relationship and interaction between bacteria and host. Key words Legionella pneumophila; intracellular growth; morphological characteristic; invasionLegionella pneumophila is a bacterium that is ubiquitous in natural and manmade water systems.1) It infects predominantly macrophages and lung epithelial cells leading to potentially lethal community-or hospital-acquired pneumonia. 2)A variety of cell types, including protozoa, peripheral blood mononuclear cells, epithelioid cells, and non-phagocytic cells (A549, CHO-K1, and human cervical cancer cell line (HeLa), etc.), have been used as host cells to characterize the intracellular proliferation of L. pneumophila and to study the relationship between L. pneumophila and host cells. [3][4][5] In recent years, studies using molecular and genetic approaches have revealed virulence-related genes and genetic loci that contribute to the virulence of L. pneumophila, such as the mip gene and the iraAB and dot/icm loci.6,7) The mechanisms of cell invasion and intracellular lifestyle of L. pneumophila have been described in some cell lines. 8,9) However, the difference of intracellular proliferation of L. pneumophila in each host cell line is still poorly characterized. Actually, some features are unique to the interactions between L. pneumophila and specific host cells.2) This study was undertaken to elaborate the features and expand the repertoire of cell-lines suitable to study L. pneumophila pathogenesis.In addition, breast carcinoma cell lines (MCF-7 and MDA-MB-231) harbors the expression deficiency of caspase-3 and mutated p53, respectively. Early studies indicated that the activation of caspase-3 or p53 can lead to the induction of apoptosis, 10,11) which is used by host cell to inhibit bacterial infection and intracellular proliferation. Therefore, we employed the two cell lines along with several curren...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Intracellular Growth and Morphological Characteristics of <i>Legionella pneumophila</i> during Invasion and Proliferation in Different Cells

Xiong

Yamasaki

Chen

et al. 2017

Biological & Pharmaceutical Bulletin

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“…RAW264.7 cells do not express the apoptosis-associated speck-like (ASC) adaptor protein that is an essential component of the NLRP3, AIM2, and pyrin inflammasomes but is not required for the NLRP1B inflammasome (3). Furthermore, the expression level of the NAIP/NLRC4 inflammasome in RAW264.7 cells is very low and does not become activated under our experimental conditions (31)(32)(33). We observed processing of pro-caspase-1 in wild-type cells treated with 150 or 250 mM 2DG but little processing in the NLRP1B KO line.…”

Section: Discussionmentioning

confidence: 47%

Listeria monocytogenes and Shigella flexneri Activate the NLRP1B Inflammasome

et al. 2017

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Activation of the innate immune receptor NLRP1B leads to the formation of an inflammasome, which induces autoproteolytic processing of pro-caspase-1, and ultimately to the release of inflammatory cytokines and to the execution of pyroptosis. One of the signals to which NLRP1B responds is metabolic stress that occurs in cells deprived of glucose or treated with metabolic inhibitors. NLRP1B might therefore sense microbial infection, as intracellular pathogens such as Listeria monocytogenes and Shigella flexneri cause metabolic stress as a result of nutrient scavenging and host cell damage. Here we addressed whether these pathogens activate the NLRP1B inflammasome. We found that Listeria infection activated the NLRP1B inflammasome in a reconstituted fibroblast model. Activation of NLRP1B by Listeria was diminished in an NLRP1B mutant shown previously to be defective at detecting energy stress and was dependent on the expression of listeriolysin O (LLO), a protein required for vacuolar escape. Infections of either Listeria or Shigella activated NLRP1B in the RAW264.7 murine macrophage line, which expresses endogenous NLRP1B. We conclude that NLRP1B senses cellular infection by distinct invasive pathogens.KEYWORDS Listeria monocytogenes, NLRP1B, Shigella, caspase-1, inflammasome N LRP1B is a pattern recognition receptor that forms a multiprotein complex termed an inflammasome after it detects an activating signal (1). The NLRP1B inflammasome complex consists of multiple copies of NLRP1B and pro-caspase-1. The assembly of the complex leads to autoproteolysis of pro-caspase-1 and, consequently, to processing of inflammatory cytokines interleukin-1␤ (IL-1␤) and IL-18 and to a type of cell death called pyroptosis (2, 3). NLRP1B has four domains (2) (Fig. 1A). The N-terminal NACHT domain (a domain present in NAIP, CIITA, HET-E, and TP-1) is a nucleotide-binding domain that selfassociates. The leucine-rich repeat (LRR) domain is involved in autoinhibition (4, 5), and the function to find domain (FIIND) undergoes autoproteolytic processing, which facilitates inflammasome assembly (6-8). The C-terminal caspase-activating and recruitment domain (CARD) binds the CARD of pro-caspase-1 (4).Anthrax lethal toxin is the only known direct activator of murine NLRP1B (1). The proteolytic component of the toxin cleaves NLRP1B near its N terminus; this cleavage is sufficient to relieve autoinhibition and allow oligomerization (9-11). Depletion of intracellular ATP is another activator of NLRP1B but one that probably triggers inflammasome assembly indirectly (12). The N-terminal region of NLRP1B is not cleaved after depletion of ATP, and the FIIND of NLRP1B facilitated the detection of this signal instead (5). Thus, activation of NLRP1B occurs through at least two distinct mechanisms.The intracellular parasite Toxoplasma gondii is also detected by NLRP1B (13,14), although the direct signal has not been determined. It is possible that Toxoplasma infection causes a reduction in cytosolic ATP. Notably, the parasite cannot synthesiz...

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“…The transition from a replicative phase to a transmissive phase prior to egress coincides with the activation of several virulence traits, including motility and the production of flagellin (17). Cytosolic flagellin induces a proinflammatory response that leads to host cell death through the activation of Naip/Nlrc1 and caspase-1-mediated pyroptosis (59)(60)(61)(62). L. pneumophila may exploit this pathway for egress, whereby activation of the flagellar regulon at late stages of infection triggers host cell lysis and the release of bacteria.…”

Section: Discussionmentioning

confidence: 99%

Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila

et al. 2016

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dLegionella pneumophila is an intracellular bacterial pathogen that replicates in alveolar macrophages, causing a severe form of pneumonia. Intracellular growth of the bacterium depends on its ability to sequester iron from the host cell. In the L. pneumophila strain 130b, one mechanism used to acquire this essential nutrient is the siderophore legiobactin. Iron-bound legiobactin is imported by the transport protein LbtU. Here, we describe the role of LbtP, a paralog of LbtU, in iron acquisition in the L. pneumophila strain Philadelphia-1. Similar to LbtU, LbtP is a siderophore transport protein and is required for robust growth under iron-limiting conditions. Despite their similar functions, however, LbtU and LbtP do not contribute equally to iron acquisition. The Philadelphia-1 strain lacking LbtP is more sensitive to iron deprivation in vitro. Moreover, LbtP is important for L. pneumophila growth within macrophages while LbtU is dispensable. These results demonstrate that LbtP plays a dominant role over LbtU in iron acquisition. In contrast, loss of both LbtP and LbtU does not impair L. pneumophila growth in the amoebal host Acanthamoeba castellanii, demonstrating a host-specific requirement for the activities of these two transporters in iron acquisition. The growth defect of the ⌬lbtP mutant in macrophages is not due to alterations in growth kinetics. Instead, the absence of LbtP limits L. pneumophila replication and causes bacteria to prematurely exit the host cell. These results demonstrate the existence of a preprogrammed exit strategy in response to iron limitation that allows L. pneumophila to abandon the host cell when nutrients are exhausted.

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The human apoptosis inhibitor NAIP induces pyroptosis in macrophages infected with Legionella pneumophila

Cited by 31 publications

References 39 publications

Intracellular Growth and Morphological Characteristics of <i>Legionella pneumophila</i> during Invasion and Proliferation in Different Cells

Intracellular Growth and Morphological Characteristics of <i>Legionella pneumophila</i> during Invasion and Proliferation in Different Cells

Listeria monocytogenes and Shigella flexneri Activate the NLRP1B Inflammasome

Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila

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