scholarly journals Adequate Expression of Protective Immunity in the Absence of Granuloma Formation in Mycobacterium tuberculosis-Infected Mice with a Disruption in the Intracellular Adhesion Molecule 1 Gene

1998 ◽  
Vol 66 (4) ◽  
pp. 1666-1670 ◽  
Author(s):  
Christine M. Johnson ◽  
Andrea M. Cooper ◽  
Anthony A. Frank ◽  
Ian M. Orme

ABSTRACT It remains unknown whether the expression of cell-mediated protective immunity and the capacity to mount a delayed-type hypersensitivity (DTH) reaction in tuberculosis infection represent two manifestations of a basic response or are dissociable events. In this study, we present data in favor of the latter hypothesis, by showing that tuberculosis infection in the lungs of mice possessing only a truncated form of intracellular adhesion molecule 1 due to gene disruption was still adequately controlled by the expression of protective immunity in the absence of any sustained influx of macrophages and the lack of formation of appreciable granulomas. These animals also had no detectable DTH response to mycobacterial proteins in the footpad assay, indicating that the accumulation of blood-borne macrophages at sites of mycobacterial infection or antigen deposition is not essential to control of the infection. These data support the hypothesis that the DTH component of the cellular response is not protective but contributes by walling off the sites of infection to prevent dissemination and reactivation disease.

2012 ◽  
Vol 19 (5) ◽  
pp. 723-730 ◽  
Author(s):  
Xiaoman Li ◽  
Wei Xu ◽  
Sidong Xiong

ABSTRACTTuberculosis (TB) caused byMycobacterium tuberculosisremains a major infectious disease worldwide. Moreover, latentM. tuberculosisinfection is more likely to progress to active TB and eventually leads to death when HIV infection is involved. Thus, it is urgent to develop a novel TB vaccine with immunogenicity to bothM. tuberculosisand HIV. In this study, four uncharacterized T cell epitopes from MPT64, Ag85A, Ag85B, and TB10.4 antigens ofM. tuberculosiswere predicted, and HIV-1-derived p24, an immunodominant protein that can induce protective responses to HIV-1, was used as an immunogenic backbone.M. tuberculosisepitopes were incorporated separately into the gene backbone of p24, forming a pP24-Mtb DNA vaccine. We demonstrated that pP24-Mtb immunization induced a strongM. tuberculosis-specific cellular response as evidenced by T cell proliferation, cytotoxicity, and elevated frequency of gamma interferon (IFN-γ)-secreting T cells. Interestingly, a p24-specific cellular response and high levels of p24-specific IgG were also induced by pP24-Mtb immunization. When the protective effect was assessed after mycobacterial challenge, pP24-Mtb vaccination significantly reduced tissue bacterial loads and profoundly attenuated the mycobacterial infection-related lung inflammation and injury. Our findings demonstrated that the pP24-Mtb tuberculosis vaccine confers effective protection against mycobacterial challenge with simultaneously elicited robust immune responses to HIV-1, which may provide clues for developing novel vaccines to prevent dual infections.


2014 ◽  
Vol 32 (1) ◽  
pp. 04-10 ◽  
Author(s):  
Marcelo Genofre Vallada ◽  
Thelma Suely Okay ◽  
Gilda Maria B. Del Negro ◽  
Claudio Amaral Antonio ◽  
Lidia Yamamoto ◽  
...  

Objective: To evaluate the accuracy of an interferongamma release assay (QuantiFERON-TB Gold in Tube) for diagnosing Mycobacterium tuberculosis infection in a young pediatric population. Methods: 195 children previously vaccinated with BCG were evaluated, being 184 healthy individuals with no clinical or epidemiological evidence of mycobacterial infection, and 11 with Mycobacterium tuberculosis infection, according to clinical, radiological, and laboratory parameters. A blood sample was obtained from each child and processed according to the manufacturer's instructions. The assay performance was evaluated by a Receiver Operating Characteristic (ROC) curve. Results: In the group of 184 non-infected children, 130 (70.6%) were under the age of four years (mean age of 35 months). In this group, 177 children (96.2%) had negative test results, six (3.2%) had indeterminate results, and one (0.5%) had a positive result. In the group of 11 infected children, the mean age was 58.5 months, and two of them (18%) had negative results. The ROC curve had an area under the curve of 0.88 (95%CI 0.82-0.92; p<0.001), disclosing a predictive positive value of 81.8% for the test (95%CI 46.3-97.4). The assay sensitivity was 81.8% (95%CI 48.2-97.2) and the specificity was 98.8% (95%CI 96-99.8). Conclusions: In the present study, the QuantiFERON-TB Gold in Tube performance for diagnosing M. tuberculosis infection was appropriate in a young pediatric population.


2012 ◽  
Vol 42 (4) ◽  
pp. 870-879 ◽  
Author(s):  
Gillian L. Beamer ◽  
Joshua Cyktor ◽  
David K. Flaherty ◽  
Paul C. Stromberg ◽  
Bridget Carruthers ◽  
...  

2016 ◽  
Vol 4 (4) ◽  
pp. 401-412 ◽  
Author(s):  
Masayuki Umemura ◽  
Yuko Okamoto‐Yoshida ◽  
Ayano Yahagi ◽  
Seigo Touyama ◽  
Susumu Nakae ◽  
...  

PLoS ONE ◽  
2008 ◽  
Vol 3 (8) ◽  
pp. e2869 ◽  
Author(s):  
Nasir Salam ◽  
Shashank Gupta ◽  
Sachin Sharma ◽  
Shweta Pahujani ◽  
Aprajita Sinha ◽  
...  

2018 ◽  
Vol 14 (8) ◽  
pp. e1007266 ◽  
Author(s):  
Shengfeng Hu ◽  
Xialin Du ◽  
Yulan Huang ◽  
Yuling Fu ◽  
Yalong Yang ◽  
...  

2007 ◽  
Vol 76 (3) ◽  
pp. 935-941 ◽  
Author(s):  
Bruno Rivas-Santiago ◽  
Rogelio Hernandez-Pando ◽  
Claudia Carranza ◽  
Esmeralda Juarez ◽  
Juan Leon Contreras ◽  
...  

ABSTRACT The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.


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