The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Microenvironments in Tuberculous Granulomas Are Delineated by Distinct Populations of Macrophage Subsets and Expression of Nitric Oxide Synthase and Arginase Isoforms
Open accessAbstract
Macrophages in granulomas are both antimycobacterial effector and host cell for Mycobacterium tuberculosis, yet basic aspects of macrophage diversity and function within the complex structures of granulomas remain poorly understood. To address this, we examined myeloid cell phenotypes and expression of enzymes correlated with host defense in macaque and human granulomas. Macaque granulomas had upregulated inducible and endothelial NO synthase (iNOS and eNOS) and arginase (Arg1 and Arg2) expression and enzyme activity compared with nongranulomatous tissue. Immunohistochemical analysis indicated macrophages adjacent to uninvolved normal tissue were more likely to express CD163, whereas epithelioid macrophages in regions where bacteria reside strongly expressed CD11c, CD68, and HAM56. Calprotectin-positive neutrophils were abundant in regions adjacent to caseum. iNOS, eNOS, Arg1, and Arg2 proteins were identified in macrophages and localized similarly in granulomas across species, with greater eNOS expression and ratio of iNOS/Arg1 expression in epithelioid macrophages as compared with cells in the lymphocyte cuff. iNOS, Arg1, and Arg2 expression in neutrophils was also identified. The combination of phenotypic and functional markers support that macrophages with anti-inflammatory phenotypes localized to outer regions of granulomas, whereas the inner regions were more likely to contain macrophages with proinflammatory, presumably bactericidal, phenotypes. Together, these data support the concept that granulomas have organized microenvironments that balance antimicrobial anti-inflammatory responses to limit pathology in the lungs.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
The many faces of macrophage activation
Mosser, D. M. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0602325 · Cited by 1,902 · cited 1×
“macrophage polarization occurs on a spectrum (27) with classical and alternative activation on opposing ends of a spectrum but with most macrophages having characteristics somewhere along that continuum.”
BackgroundAn interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis
Berry, M. P. R., Graham, C. M., McNab, F. W., Xu, Z., Bloch, S. A. A., Oni, T., Wilkinson, K. A., Banchereau, R., Skinner, J., Wilkinson, R. J., et al. (2010) · Nature · doi:10.1038/nature09247 · Cited by 1,898
Nathan, C., & Shiloh, M. U. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.8841 · Cited by 1,469
Identification of nitric oxide synthase as a protective locus against tuberculosis
MacMicking, J. D., North, R. J., LaCourse, R., Mudgett, J. S., Shah, S. K., & Nathan, C. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5243 · Cited by 1,180
El Kasmi, K. C., Qualls, J. E., Pesce, J. T., Smith, A. M., Thompson, R. W., Henao-Tamayo, M., Basaraba, R. J., König, T., Schleicher, U., Koo, M.-S., et al. (2008) · Nature Immunology · doi:10.1038/ni.1671 · Cited by 646 · cited 1×
“tuberculosis infection in mice (23, 24), likely reflecting depletion of L-arginine substrate for NO synthesis.”
BackgroundMishra, B. B., Rathinam, V. A. K., Martens, G. W., Martinot, A. J., Kornfeld, H., Fitzgerald, K. A., & Sassetti, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2474 · Cited by 571
Neutrophils in tuberculosis: friend or foe?
Lowe, D. M., Redford, P. S., Wilkinson, R. J., O’Garra, A., & Martineau, A. R. (2012) · Trends in Immunology · doi:10.1016/j.it.2011.10.003 · Cited by 312
Cited by
Nitric oxide synthase in innate and adaptive immunity: an update
Bogdan, C. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.01.003 · Cited by 862
Inflammatory signaling in human tuberculosis granulomas is spatially organized
Marakalala, M. J., Raju, R. M., Sharma, K., Zhang, Y. J., Eugenin, E. A., Prideaux, B., Daudelin, I. B., Chen, P.-Y., Booty, M. G., Kim, J. H., et al. (2016) · Nature Medicine · doi:10.1038/nm.4073 · Cited by 308
Self-citationHow sisters grow apart: mycobacterial growth and division
Kieser, K. J., & Rubin, E. J. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3299 · Cited by 268
Salim, T., Sershen, C. L., & May, E. E. (2016) · PLOS ONE · doi:10.1371/journal.pone.0153289 · Cited by 210
Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas
Duque-Correa, M. A., Kühl, A. A., Rodriguez, P. C., Zedler, U., Schommer-Leitner, S., Rao, M., Weiner, J., Hurwitz, R., Qualls, J. E., Kosmiadi, G. A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408839111 · Cited by 146
Metadata
- Authors
- Mattila, J. T., Ojo, O. O., Kepka-Lenhart, D., Marino, S., Kim, J. H., Eum, S. Y., Via, L. E., Barry, C. E., Klein, E., Kirschner, D. E., Morris, S. M., Lin, P. L., & Flynn, J. L.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-07
- Volume
- 191
- Issue
- 2
- Pages
- 773-784
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2109531704
- Cited by
- 347
- References
- 11
- FWCI
- 22.44
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Microenvironments in Tuberculous Granulomas Are Delineated by Distinct Populations of Macrophage Subsets and Expression of Nitric Oxide Synthase and Arginase Isoforms. https://app.cochat.ai/papers/10.4049/jimmunol.1300113
- The paper
- Mattila, J. T., Ojo, O. O., Kepka-Lenhart, D., Marino, S., Kim, J. H., Eum, S. Y., Via, L. E., Barry, C. E., Klein, E., Kirschner, D. E., Morris, S. M., Lin, P. L., & Flynn, J. L. (2013). Microenvironments in Tuberculous Granulomas Are Delineated by Distinct Populations of Macrophage Subsets and Expression of Nitric Oxide Synthase and Arginase Isoforms. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1300113
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
