Abstract:
:Human genital Chlamydia infection is a major public health concern due to the serious reproductive system complications. Chlamydia binds several receptor tyrosine kinases (RTKs) on host cells, including the epidermal growth factor receptor (EGFR), and activates cellular signaling cascades for host invasion, cytoskeletal remodeling, optimal inclusion development, and induction of pathogenic epithelial-mesenchyme transition (EMT). Chlamydia also upregulates transforming growth factor beta (TGF-β) expression, whose signaling pathway synergizes with the EGFR cascade, but its role in infectivity, inclusions, and EMT induction is unknown. We hypothesized that the EGFR and TGF-β signaling pathways cooperate during chlamydial infection for optimal inclusion development and stable EMT induction. The results revealed that Chlamydia upregulated TGF-β expression as early as 6 h postinfection of epithelial cells and stimulated both the EGFR and TGF-β signaling pathways. Inhibition of either the EGFR or TGF-βR1 signaling substantially reduced inclusion development; however, the combined inhibition of both EGFR and TGF-βR1 signaling reduced inclusions by over 90% and prevented EMT induction. Importantly, EGFR inhibition suppressed TGF-β expression, and an inhibitory thrombospondin-1 (Tsp1)-based peptide inhibited chlamydia-induced EMT, revealing a major source of active TGF-β during infection. Finally, TGF-βR signaling inhibition suppressed the expression of transforming acidic coiled-coil protein-3 (TACC3), which stabilizes EGFR signaling, suggesting reciprocal regulation between TGF-β and EGFR signaling during chlamydial infection. Thus, RTK-mediated host invasion by chlamydia upregulated TGF-β expression and signaling, which cooperated with other cellular signaling cascades and cytoskeletal remodeling to support optimal inclusion development and EMT induction. This finding may provide new targets for chlamydial disease biomarkers and prevention.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Igietseme JU,Partin J,George Z,Omosun Y,Goldstein J,Joseph K,Ellerson D,Eko FO,Pohl J,Bandea C,Black CMdoi
10.1128/IAI.00819-19subject
Has Abstractpub_date
2020-03-23 00:00:00issue
4eissn
0019-9567issn
1098-5522pii
IAI.00819-19journal_volume
88pub_type
杂志文章abstract::In vivo administration of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) to mice induced apoptosis before a specific immune response. Apoptosis was associated with the expression of immunoglobulin and Ia on B cells and of CD5 and several markers on T cells. Apoptosis peaked in the spleen and lymph nodes on day 2...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.64.4.1461-1466.1996
更新日期:1996-04-01 00:00:00
abstract::Minicells are small, anucleate cells resulting from aberrant cell divisions at the polar ends of bacilli. We have isolated minicell-producing mutant strains of Shigella flexneri 2a (MC-I) and Shigella dysenteriae 1 (MC-V) after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Microscopically, broth cultures of M...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.30.1.297-302.1980
更新日期:1980-10-01 00:00:00
abstract::Ultrastructural changes in cells of the mouse footpad are described which occurred during the log phase of multiplication, the plateau, and the stationary phase of growth of Mycobacterium leprae.BALB/c mice were inoculated in the right hind footpad with 5 x 10(3) organisms and sacrificed in pairs at 86 to 173 days aft...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.5.2.238-247.1972
更新日期:1972-02-01 00:00:00
abstract::Sixty-one Burkholderia cepacia isolates from patients with cystic fibrosis (CF) and four plant isolates were screened for production of the siderophores salicylic acid (SA), pyochelin, cepabactin, and ornibactins and fingerprinted by a PCR-based randomly amplified polymorphic DNA (RAPD) method. Of the 24 RAPD types de...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.2.874-877.1998
更新日期:1998-02-01 00:00:00
abstract::It was demonstrated that complement-coated sheep erythrocytes bind to Candida albicans cells grown in serum-free RPMI 1640 medium. Testing of purified complement components proved that iC3b and C3d were responsible for the reaction, whereas C3b and C3b-H reacted only slightly if at all. Binding occurred only to C. alb...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.50.2.598-600.1985
更新日期:1985-11-01 00:00:00
abstract::Burkholderia pseudomallei is a CDC tier 1 select agent that causes melioidosis, a severe disease in humans and animals. Persistent infections are common, and there is currently no vaccine available. Lipopolysaccharide (LPS) is a potential vaccine candidate. B. pseudomallei expresses three serologically distinct LPS ty...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.02785-14
更新日期:2015-05-01 00:00:00
abstract::Heat shock protein (HSP) expression was examined in murine bone marrow-derived macrophages infected with stationary-phase promastigotes of Leishmania donovani. Immunoblotting performed with a rabbit polyclonal antiserum raised against HSP60 from Heliothis virescens (moth) revealed the de novo appearance of 65- and 67-...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.8.3265-3272.1993
更新日期:1993-08-01 00:00:00
abstract::Bacterial overgrowth in the small bowel is known to occur in patients with persistent diarrhea, but it has been unclear if colonization alone causes fluid secretion. We studied isogenic, nontoxigenic Escherichia coli strains with colonizing factor antigen II (CFA/II) (1392+) and without CFA/II (1392-) in 18-h rabbit i...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.8.1924-1926.1987
更新日期:1987-08-01 00:00:00
abstract::Organisms of the Mycobacterium avium complex are associated with disseminated infection in patients with AIDS. The mechanisms that account for the survival of the intracellular bacteria are unknown. We document here that infection of C57BL/6 black mice with M. avium 101 triggered interleukin-10 (IL-10) production. The...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.7.3093-3097.1993
更新日期:1993-07-01 00:00:00
abstract::Natural killer (NK) cells are critically involved in the early immune response against various intracellular pathogens, including Coxiella burnetii and Chlamydia psittaciChlamydia-infected NK cells functionally mature, induce cellular immunity, and protect themselves by killing the bacteria in secreted granules. Here,...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00172-20
更新日期:2020-10-19 00:00:00
abstract::gammaG-globulin from nonimmunized rabbits and from rabbits immunized with various bacteria reacted in the immunofluorescence technique with protein A-containing Staphylococcus aureus. Pepsin digestion of most immunoglobulin preparations eliminated the reaction, thus showing that the Fc fragment is involved and that th...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.2.4.387-391.1970
更新日期:1970-10-01 00:00:00
abstract::In vitro experimentation indicates that periodontitis-associated bacteria contain potent polyclonal B-cell activators (PBA). We reasoned that if PBA were operative in vivo, plasma cells specific for nonoral antigens should be present in the inflamed gingival tissues, which are characterized by a plasma cell infiltrate...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.4.823-830.1988
更新日期:1988-04-01 00:00:00
abstract::PspA is an antigenically variable surface protein of Streptococcus pneumoniae that appears to be essential for full pneumococcal virulence. In addition, monoclonal antibodies to PspA protect mice against infection with specific strains of pneumococci virulent for mice. In this study, we have isolated the 43-kDa N-term...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.4.1285-1289.1991
更新日期:1991-04-01 00:00:00
abstract::Antigens extracted from cells of Streptococcus pyogenes T6 and Streptococcus mutans strains AHT, BHT, 10449, OMZ175, and K1R adsorbed to the sarcolemmal sheath of cardiac muscle cells in vitro. Similar preparations from S. salivarius, S. sanguis, Staphylococcus aureus, and Lactobacillus casei had weak or negligible ti...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.27.2.604-613.1980
更新日期:1980-02-01 00:00:00
abstract::The protection and immune response to infection caused by the parasite Schistosoma mansoni were studied by comparison of two murine irradiated-vaccine models. Mice were exposed from 1 to 4 times to infective-stage cercariae attenuated with either a moderate dose (15 kilorads) or a high dose (50 kilorads) of radiation....
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.1.90-94.1992
更新日期:1992-01-01 00:00:00
abstract::Immunoglobulin G (IgG)- and IgM-specific antibody titers against Salmonella typhi Ty2 porins have been measured in 30 paired typhoid sera by enzyme-linked immunosorbent assay. These studies have found that IgG serum titers of acute and convalescent sera were 625 and 5,000 times higher, respectively than the control se...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.52.1.209-212.1986
更新日期:1986-04-01 00:00:00
abstract::Candida albicans biofilms are formed through three distinct developmental phases and are associated with high fluconazole (FLU) resistance. In the present study, we used a set of isogenic Candida strains lacking one or more of the drug efflux pumps Cdr1p, Cdr2p, and Mdr1p to determine their role in FLU resistance of b...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.71.8.4333-4340.2003
更新日期:2003-08-01 00:00:00
abstract::Studies of meningococcal pathogenesis have been severely restricted due to the absence of an adequate animal model. Given the significance of iron in meningococcal pathogenesis, we developed a model of Neisseria meningitidis colonization in outbred adult mice that included daily administration of iron dextran. While r...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.71.4.1849-1855.2003
更新日期:2003-04-01 00:00:00
abstract::Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokine...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::The Bordetella pertussis BrkA protein protects against the bactericidal activity of complement and antibody; however, some individuals mount an immune response that overcomes this bacterial defense. To further characterize this process, the bactericidal activities of sera from 13 adults with different modes of exposur...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.3.1424-1431.1999
更新日期:1999-03-01 00:00:00
abstract::The theoretic basis for developing conjugate vaccines, to induce immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the prevention of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific polysaccharides (O-SPs) of Shigella dysent...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.9.3678-3687.1993
更新日期:1993-09-01 00:00:00
abstract::The complete sequence analysis of the 210-kb Shigella flexneri 5a virulence plasmid was determined. Shigella spp. cause dysentery and diarrhea by invasion and spread through the colonic mucosa. Most of the known Shigella virulence determinants are encoded on a large plasmid that is unique to virulent strains of Shigel...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.5.3271-3285.2001
更新日期:2001-05-01 00:00:00
abstract::Susceptibility to the lethal toxicity of endotoxin in mice pretreated with emulsified trehalose-6,6'-dimycolate was enhanced by (i) increasing the oil concentration while keeping the Tween concentration constant; and (ii) decreasing the Tween concentration, while keeping the oil concentration constant. ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.24.2.571-572.1979
更新日期:1979-05-01 00:00:00
abstract::Neisseria meningitidis is a major cause of sepsis and meningitis but is also a common commensal, present in the nasopharynx of between 8 and 20% of healthy individuals. During carriage, the bacterium is found on the surface of the nasopharyngeal epithelium and in deeper tissues, while to develop disease the meningococ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01377-09
更新日期:2010-09-01 00:00:00
abstract::Streptococcal pyrogenic exotoxin B (SpeB), a conserved cysteine protease expressed by virtually all Streptococcus pyogenes strains, has recently been shown to be an important virulence factor (S. Lukomski, S. Sreevatsan, C. Amberg, W. Reichardt, M. Woischnik, A. Podbielski, and J. M. Musser, J. Clin. Invest. 99:2574-2...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.2.771-776.1998
更新日期:1998-02-01 00:00:00
abstract::Immunofluorescence microscopy demonstrated that laminin bound to the surface of Penicillium marneffei conidia. Attachment of P. marneffei conidia in an adherence assay was inhibited by soluble laminin and anti-laminin antibody. N-Acetylneuraminic acid abolished adherence, indicating an interaction mediated by a sialic...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.12.6024-6026.1998
更新日期:1998-12-01 00:00:00
abstract::The genes of the lic1 operon (lic1A to lic1D) are responsible for incorporation of phosphocholine (PCho) into the lipopolysaccharide (LPS) of Haemophilus influenzae. PCho plays a multifaceted role in the commensal and pathogenic lifestyles of a range of mucosal pathogens, including H. influenzae. Structural studies of...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00748-07
更新日期:2008-02-01 00:00:00
abstract::Strains of type III group B streptococci isolated from patients with neonatal sepsis are generally resistant to complement-mediated phagocytic killing in the absence of specific antibody. It has been suggested that the resistance of type III group B streptococci to phagocytosis results from inhibition of alternative-c...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.10.3986-3993.1992
更新日期:1992-10-01 00:00:00
abstract::Burkholderia cenocepacia, a member of the B. cepacia complex, is an opportunistic pathogen that causes serious infections in patients with cystic fibrosis. We identified a six-gene cluster in chromosome 1 encoding a two-component regulatory system (BCAL2831 and BCAL2830) and an HtrA protease (BCAL2829) hypothesized to...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01581-06
更新日期:2007-04-01 00:00:00
abstract::A fibronectin-binding protein (FnBP) adhesin of Staphylococcus aureus possesses three 37- or 38-amino-acid motifs (D1, D2, and D3) that can each bind fibronectin (Fn) with low affinity and that in tandem comprise D1-3, a high-affinity Fn-binding domain. To identify epitopes for the generation of adhesion-blocking anti...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.65.2.537-543.1997
更新日期:1997-02-01 00:00:00