Abstract:
:The hallmarks of pulmonary Mycobacterium tuberculosis infection are lung granulomas. These organized structures are composed of host immune cells whose purpose is to contain or clear infection, creating a complex hub of immune and bacterial cell activity, as well as limiting pathology in the lungs. Yet, given cellular activity and the potential for frequent interactions between host immune cells and M. tuberculosis-infected cells, we observed a surprisingly low quantity of cytokine-producing T cells (<10% of granuloma T cells) in our recent study of M. tuberculosis infection within nonhuman primate (NHP) granulomas. Various mechanisms could limit T cell function, and one hypothesis is T cell exhaustion. T cell exhaustion is proposed to result from continual antigen stimulation, inducing them to enter a state characterized by low cytokine production, low proliferation, and expression of a series of inhibitory receptors, the most common being PD-1, LAG-3, and CTLA-4. In this work, we characterized the expression of inhibitory receptors on T cells and the functionality of these cells in tuberculosis (TB) lung granulomas. We then used these experimental data to calibrate and inform an agent-based computational model that captures environmental, cellular, and bacterial dynamics within granulomas in lungs during M. tuberculosis infection. Together, the results of the modeling and the experimental work suggest that T cell exhaustion alone is not responsible for the low quantity of M. tuberculosis-responsive T cells observed within TB granulomas and that the lack of exhaustion is likely an intrinsic property of granuloma structure.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Wong EA,Joslyn L,Grant NL,Klein E,Lin PL,Kirschner DE,Flynn JLdoi
10.1128/IAI.00426-18subject
Has Abstractpub_date
2018-08-22 00:00:00issue
9eissn
0019-9567issn
1098-5522pii
IAI.00426-18journal_volume
86pub_type
杂志文章abstract::Cryptosporidial infections in severe combined immune deficient (SCID) mice produce a chronic disease state which in the later stages leads to extraintestinal involvement and hepatic dysfunction. To further characterize the infection dynamics in this model and monitor the changes in the hepatic system, a dose titration...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.5.1691-1695.1994
更新日期:1994-05-01 00:00:00
abstract::Genome sequencing of the relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae identified three open reading frames (ORFs) on the chromosomes that contained internal, tandemly repeated amino acid sequences that were absent in the Lyme disease spirochete Borrelia burgdorferi. The predicted amino acid sequ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.5.3025-3037.2005
更新日期:2005-05-01 00:00:00
abstract::The ability to bind Congo red (Crb+) is associated with virulence of Shigella flexneri and is encoded by a large, 220-kilobase plasmid. We cloned fragments of this plasmid to isolate the sequences encoding Congo red binding, to determine the degree of conservation of these sequences among S. flexneri strains, and to s...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.54.2.435-443.1986
更新日期:1986-11-01 00:00:00
abstract::The method of hemagglutination inhibition was used to investigate the antigenic diversity of lipopolysaccharide (LPS) from Neisseria meningitidis and to develop a serotyping systems based on this antigen. The system uses outer membrane complex prepared by a simple extraction procedure to inhibit homologous hemagglutin...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.16.2.471-475.1977
更新日期:1977-05-01 00:00:00
abstract::Toxoplasma gondii is a protozoan parasite that is able to penetrate human monocytes by either passive uptake during phagocytosis or active penetration. It is expected that immunoglobulin G (IgG) opsonization will target the parasite to macrophage Fc gamma receptors for phagocytic processing and subsequent degradation....
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.63.11.4290-4294.1995
更新日期:1995-11-01 00:00:00
abstract::A plaque assay system for pathogenic rickettsiae, which utilizes primary chick embryo tissue cultures, is described. It proved to be a highly reproducible measure of infectiousness for Rickettsia rickettsi and R. typhi, which were employed in most studies; as well as for R. canada, R. prowazeki, R. sibirica, R. akari,...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.5.5.715-722.1972
更新日期:1972-05-01 00:00:00
abstract::In an earlier report, we had described the isolation and characterization of autolysis-defective mutants of Staphylococcus aureus (N. Mani, P. Tobin, and R.K. Jayaswal, J. Bacteriol. 175:1493-1499, 1993). In the study reported here, an autolysis-defective mutant showed attenuated virulence in a rat model of experiment...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.4.1406-1409.1994
更新日期:1994-04-01 00:00:00
abstract::Previous studies indicated that inorganic pyrophosphatase of Ascaris suum (AsPPase) plays an important role in larval survival in the host. Here we describe a precise role for AsPPase in larval molting and development and also describe the potential role of recombinant AsPPase (rAsPPase) in protective immunity to A. s...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.4.1995-2004.2005
更新日期:2005-04-01 00:00:00
abstract::Salmonella enterica serovar Typhimurium causes self-limiting gastroenteritis in humans and a typhoid-like disease in mice that serves as a model for typhoid infections in humans. A critical step in Salmonella pathogenesis is the invasion of enterocytes and M cells of the small intestine via expression of a type III se...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.72.4.2002-2013.2004
更新日期:2004-04-01 00:00:00
abstract::Mice orally immunized with Salmonella dublin EL23, a nonreverting, aromatic-dependent, histidine-requiring mutant transformed with a plasmid which carries a gene that codes for production of the B subunit of the heat-labile toxin (LT-B) of enterotoxigenic Escherichia coli, or with purified LT-B alone were compared for...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.63.3.1076-1083.1995
更新日期:1995-03-01 00:00:00
abstract::Previous studies found that normal human serum (NHS) contains an immunoglobulin G (IgG) antibody that mediates initiation of the classical complement pathway by nonencapsulated Cryptococcus neoformans. The present study used an enzyme-linked immunosorbent assay with whole nonencapsulated yeast cells as solid-phase ant...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.1.215-220.1994
更新日期:1994-01-01 00:00:00
abstract::BCG, the attenuated strain of Mycobacterium bovis, has been widely used as a vaccine against tuberculosis and is thus an important candidate as a live carrier for multiple antigens. With the aim of developing a recombinant BCG (rBCG) vaccine against diphtheria, pertussis, and tetanus (DPT), we analyzed the potential o...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.2.869-874.2001
更新日期:2001-02-01 00:00:00
abstract::The virulence of Candida albicans in a mouse model of invasive candidiasis is dependent on the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE). Disruption of the PS synthase gene CHO1 (i.e., cho1Δ/Δ) eliminates PS and blocks the de novo pathway for PE biosynthesis. In addition, the cho1Δ/Δ muta...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01612-14
更新日期:2014-10-01 00:00:00
abstract::Accurate diagnosis and early treatment of tuberculosis (TB) and latent TB infection (LTBI) are vital to prevent and control TB. The lack of specific biomarkers hinders these efforts. This study's purpose was to screen immunological markers that discriminate Mycobacterium tuberculosis infection outcomes in a setting wh...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00759-17
更新日期:2018-03-22 00:00:00
abstract::A Pasteurella haemolytica mutant incapable of producing leukotoxin was created by allelic replacement. Concentrated culture supernatants from wild-type P. haemolytica, but not from the mutant, contained the 102-kDa leukotoxin protein and lysed bovine lymphoma cells and sheep erythrocytes. Wild-type P. haemolytica demo...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.63.8.3209-3212.1995
更新日期:1995-08-01 00:00:00
abstract::The ability of butyric acid, an extracellular metabolite from periodontopathic bacteria, to induce apoptosis in murine WEHI 231 cells, splenic B cells, and human RAJI cells was examined. The culture filtrate of Porphyromonas gingivalis, Prevotella loescheii, and Fusobacterium nucleatum, which contains high a percentag...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.6.2587-2594.1998
更新日期:1998-06-01 00:00:00
abstract::The two enteropathogens Yersinia pseudotuberculosis and Yersinia enterocolitica penetrate eukaryotic cells in vitro through invasin, a surface-exposed protein. In contrast, Yersinia pestis, the causative agent of plague, is unable to enter mammalian cell lines, although the inv gene is present on its chromosome. Altho...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.64.1.375-379.1996
更新日期:1996-01-01 00:00:00
abstract::Localized juvenile periodontosis is associated with a defect of neutrophil chemotaxis that is characterized by selective depletion of a surface protein with a molecular mass of 110 kDa (GP110). Data on partial characterization of GP110 suggest that it is a glycoprotein which is enriched in Lys, Glu, His, Leu, and Ala ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.7.3015-3016.1992
更新日期:1992-07-01 00:00:00
abstract::Infection with highly pathogenic Streptococcus suis can cause septic shock, which is characterized by high levels of inflammatory cytokines and a high mortality rate. Our previous study indicated that TREM-1 (triggering receptor expressed on myeloid cells 1) was upregulated in swine spleen cells in response to S. suis...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00440-15
更新日期:2015-08-01 00:00:00
abstract::Murine bone marrow-derived dendritic cells (DC) can phagocytose and process Salmonella enterica serovar Typhimurium for peptide presentation on major histocompatibility complex class I (MHC-I) and MHC-II molecules. To investigate if a serovar Typhimurium encounter with DC induces maturation and downregulates their abi...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.68.11.6311-6320.2000
更新日期:2000-11-01 00:00:00
abstract::Klebsiella pneumoniae strains typically express both smooth lipopolysaccharide (LPS) with O antigen molecules and capsule polysaccharide (K antigen) on the surface. A single mutation in a gene that codes for a UDP galacturonate 4-epimerase (uge) renders a strain with the O-:K- phenotype (lack of capsule and LPS withou...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.72.1.54-61.2004
更新日期:2004-01-01 00:00:00
abstract::Results of earlier investigations have indicated that the saprobic phase of Coccidioides immitis produces a heat-stable, 19-kDa antigen with serine proteinase activity which has been suggested to be specific for this pathogenic fungus. In the present study we have determined the N-terminal and partial internal amino a...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.63.10.3994-4002.1995
更新日期:1995-10-01 00:00:00
abstract::A total of 32 patients with Plasmodium falciparum malaria were studied. Of these, 23 had benign infections, and 9 had typical cerebral malaria. Cryoglobulins, circulating immune complexes detected by a C1q-binding assay, and hypocomplementemia were found in eight of nine patients with cerebral malaria. Raised levels o...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.31.2.530-535.1981
更新日期:1981-02-01 00:00:00
abstract::Very little is known about the host response to chlamydial genital infection in the male, particularly about the nature of the local response in the urethra. In this study, the pathological and immunologic responses to urethral infection of the male guinea pig with Chlamydia caviae (Chlamydophila caviae) were characte...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01339-09
更新日期:2010-04-01 00:00:00
abstract::The purified recombinant V antigen from Yersinia pestis, expressed in Escherichia coli and adsorbed to aluminum hydroxide, an adjuvant approved for human use, was used to immunize outbred Hsd:ND4 mice subcutaneously. Immunization protected mice from lethal bubonic and pneumonic plague caused by CO92, a wild-type F1+ s...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.64.11.4580-4585.1996
更新日期:1996-11-01 00:00:00
abstract::In studies of immunity to malaria, the absence of febrile malaria is commonly considered evidence of "protection." However, apparent "protection" may be due to a lack of exposure to infective mosquito bites or due to immunity. We studied a cohort that was given curative antimalarials before monitoring began and docume...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01358-08
更新日期:2009-05-01 00:00:00
abstract::Immunoprecipitation of radiolabeled antigens with bovine antisera indicated that many Babesia bigemina and Babesia bovis merozoite proteins contain isolate-common epitopes, while at least 16 B. bigemina and 8 B. bovis proteins contain species-cross-reactive epitopes. One immunogenic, isolate-common, and species-specif...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.6.1658-1660.1988
更新日期:1988-06-01 00:00:00
abstract::Trehalose 6,6'-dimycolate (TDM) plays important roles in the development of granulomatous inflammation during infection with Mycobacterium spp., Rhodococcus spp., etc. To reveal the augmenting effect of TDM on vascular endothelial growth factor (VEGF) production and neovascularization, we investigated murine granuloma...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.68.4.2043-2052.2000
更新日期:2000-04-01 00:00:00
abstract::Earlier work had shown that a collection of anaerobic bacteria, in conjunction with facultative anaerobes, may be implanted into germfree mice, thereby rendering the animals "normal" with respect to a variety of parameters tested. The present experiments indicate that a different collection of anaerobic bacteria, isol...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.6.2.119-126.1972
更新日期:1972-08-01 00:00:00
abstract::Antibodies against feline leukemia virus (FeLV) and the feline oncornavirus-associated cell membrane antigen (FOCMA) were transferred from pregnant cats to their suckling kittens. All of these kittens were protected against infection and oncogenesis by virulent FeLV when challenged at 2 weeks of age. Suckling kittens ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.16.1.54-59.1977
更新日期:1977-04-01 00:00:00