Granulocyte–macrophage colony stimulating factor-mediated innate responses in tuberculosis

Szeliga, Jacek; Daniel, Deepu; Yang, Ching; Sever-Chroneos, Zvjezdana; Jagannath, Chinnaswamy; Chroneos, Zissis C.

doi:10.1016/j.tube.2007.08.009

Cited by 63 publications

(91 citation statements)

References 58 publications

(92 reference statements)

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“…1), suggests that fine control of GM-CSF may be required to adequately fight chronic bacterial infections and avoid prolonged inflammation. Short-term persistence of BCG:GM-CSF in vivo may be sufficient to adequately stimulate immune function, without the immunopathology associated with sustained production of GM-CSF within the lung itself [14,15], or non-organ-specific, transgenic expression of the cytokine [27]. It is also clear that targeted delivery of GM-CSF to the lung is crucial for the protective effect of the vaccine, as we observed no improved protection in the lung when BCG was administered subcutaneously, even at 4 wk post-vaccination where BCG:GM-CSF-induced protective immunity was maximal (data not shown and Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In the context of tuberculosis, GM-CSF may also contribute to the cytokine/chemokine milieu responsible for granuloma formation in the lung [14]. Over-expression of GM-CSF in the lungs impairs protective immunity against M. tuberculosis, and therefore careful regulation of pulmonary GM-CSF levels may be critical in sustaining protection against chronic tuberculosis disease [15].…”

Section: Introductionmentioning

confidence: 99%

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Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

et al. 2009

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The rational design of new vaccines engineered to target key components of the host immune response is crucial to aid control of important infectious diseases such as tuberculosis. In this report, we determined whether modifying the function of pulmonary APC could improve protection against infection with Mycobacterium tuberculosis. Targeted delivery to the lung of the cytokine GM‐CSF, expressed by the Mycobacterium bovis BCG vaccine strain, increased pulmonary DC numbers and secretion of the immunoregulatory cytokine IL‐12, compared with parental BCG immunization. This impact on APC number by BCG:GM‐CSF resulted in accelerated priming of antigen‐specific CD4+ T cells in the mediastinal lymph nodes and increased migration of activated CD4+ T cells into the lung. i.n. administration of BCG:GM‐CSF resulted in significantly increased protection against M. tuberculosis infection compared with mice vaccinated with BCG alone. BCG:GM‐CSF exhibited an improved safety profile, as immunodeficient RAG1−/− mice vaccinated i.n. with BCG:GM‐CSF survived significantly longer than control BCG‐vaccinated mice. These data demonstrate that manipulating immune cells in the lung by BCG‐based delivery of GM‐CSF can assist the development of protective mucosal immunity against pulmonary bacterial infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

et al. 2009

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“…This may be due to the bactericidal effects of the HR regimen overwhelming the host immune clearance of the bacteria, although a relatively low dose of HR was intentionally used throughout the entire experiment. However, it was reported that specific cytokines had an essential protective role in preserving alveolar structure of M. tuberculosis infected mice [28].…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis

Zhang

Liu

Wang

et al. 2012

Sci. China Life Sci.

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This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculosis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, IL-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P<0.01) and 0.58 (P<0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P<0.01) and 1.22 (P<0.01) lg CFU, respectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P<0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB). tuberculosis, MDR-TB, IL-2, GM-CSF, immunotherapy Citation:Zhang Y R, Liu J, Wang Y, et al. Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis. Sci China Life Sci, 2012, 55: 800 -806, doi: 10.1007/s11427-012-4368-x Tuberculosis (TB) remains a major public health problem worldwide [1,2]. Directly Observed Therapy-Short Course (DOTS) is the main TB control strategy recommended by the World Health Organization and has been used for many years. DOTS, when used properly, can treat 95% of drugsusceptible TB cases. However, the prevalence of multidrug resistant (MDR) and extensively drug-resistant (XDR)-TB and Mycobacterium tuberculosis/HIV co-infection make it more difficult to control TB using the DOTS strategy alone. Moreover, drug-drug interactions cause significant problems in M. tuberculosis/HIV co-infected patients. Despite the use of second-line drugs, the side effects and cost mean the rational design of new treatment regimens is required to shorten the therapeutic period, and provide a more effica-

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“…Studies in GM-CSF-deficient (GM -/-) mice showed that GM-CSF is necessary for the development of cell-mediated immunity and formation of granulomas against primary M. tuberculosis infection in the lung (71,72). Prior vaccination of mice with GM-CSF-secreting Bacillus Calmette Guerin (BCG) reduced pulmonary M. tuberculosis numbers up to 100-fold when administered locally (41,42).…”

Section: Gm-csf In Treatment Of Tuberculosismentioning

confidence: 99%

“…Furthermore, GM-CSF-deficient mice in which GM-CSF is constantly secreted at high levels by lung epithelial cells (SP-C-GM +/+ ) are resistant to the infection initially but do not sustain long-term protective immunity against tuberculosis (71,72), suggesting that high levels of GM-CSF impact cell-mediated immunity in the chronic phase of the disease. On the other hand, lack of GM-CSF in mice was detrimental for survival against virulent M. tuberculosis Rv (74) and Erdman strains (72).…”

Section: Gm-csf In Treatment Of Tuberculosismentioning

confidence: 99%

Immunoregulatory Role of GM-CSF in Pulmonary Tuberculosis

Chroneos¹,

Jagannath²

2012

Understanding Tuberculosis - Analyzing the Origin of Mycobacterium Tuberculosis Pathogenicity

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Granulocyte–macrophage colony stimulating factor-mediated innate responses in tuberculosis

Cited by 63 publications

References 58 publications

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis

Immunoregulatory Role of GM-CSF in Pulmonary Tuberculosis

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