Modeling the immune rheostat of macrophages in the lung in response to infection

Day, Judy; Friedman, Avner; Schlesinger, Larry S.

doi:10.1016/j.jcrc.2009.06.020

Cited by 29 publications

(40 citation statements)

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“…1. A similar network can be used to describe granuloma in tuberculosis (TB), although in that case one has to consider both classically activated and alternatively activated macrophages (43). However, the source of inflammation in TB arises from the TB antigen (i.e., the Mycobacterium tuberculosis); hence some of the model parameters will have to be changed in the TB case, leading to different conclusions.…”

Section: Resultsmentioning

confidence: 99%

Mathematical model of sarcoidosis

Hao

Crouser

Friedman

2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Sarcoidosis is a disease involving abnormal collection of granulomas that develop in the lung and other organs. The origin of the disease is unknown, clinical data are very limited, and there is no current effective treatment. This paper develops a mathematical model with simulations that are validated by the available clinical data. The model is then used to explore potential treatments of the disease, to suggest therapeutic targets that may reduce the disease activity, and thus to predict treatment responses in preclinical settings.

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Section: Resultsmentioning

confidence: 99%

Mathematical model of sarcoidosis

Hao

Crouser

Friedman

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Despite the progress in prevention, diagnosis, and treatment, Tuberculosis (TB) remains as one of the world's deadliest infective diseases (Global Tuberculosis Control, World Health Organization report 2014) and several lines of evidences underline the role of alternative activated/M2 macrophages in the promotion of TB pathogenesis [96][97][98][99][100], suggesting new potential therapeutic interventions.…”

Section: Mycobacterium Tuberculosis Infectionmentioning

confidence: 99%

“…Hence, AM avoid excessive lung injury, but limit defense against invading pathogens. For these reasons, during the early phase of MT infection the extent of the M1-and Th1-polarized immune response is not sufficient to radically eliminate mycobacteria [96]. Interestingly, MT can bias macrophage polarization toward an M2 polarization state through different mechanisms.…”

Section: Mycobacterium Tuberculosis Infectionmentioning

confidence: 99%

Macrophage polarization in pathology

Sica

Erreni

Allavena

et al. 2015

Cell. Mol. Life Sci.

531

422

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Macrophages are cells of the innate immunity constituting the mononuclear phagocyte system and endowed with remarkable different roles essential for defense mechanisms, development of tissues, and homeostasis. They derive from hematopoietic precursors and since the early steps of fetal life populate peripheral tissues, a process continuing throughout adult life. Although present essentially in every organ/tissue, macrophages are more abundant in the gastro-intestinal tract, liver, spleen, upper airways, and brain. They have phagocytic and bactericidal activity and produce inflammatory cytokines that are important to drive adaptive immune responses. Macrophage functions are settled in response to microenvironmental signals, which drive the acquisition of polarized programs, whose extremes are simplified in the M1 and M2 dichotomy. Functional skewing of monocyte/macrophage polarization occurs in physiological conditions (e.g., ontogenesis and pregnancy), as well as in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer) and is now considered a key determinant of disease development and/or regression. Here, we will review evidence supporting a dynamic skewing of macrophage functions in disease, which may provide a basis for macrophage-centered therapeutic strategies.

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“…Dr. Larry Schlesinger focused on the role of innate immune responses, particularly involving lung-based macrophages and dendritic cells, in mediating critical early events in Mtb pathogenesis, and emphasized the importance of understanding these early immunological responses for successful development of new TB therapeutics and vaccine strategies. The initial pulmonary immune response to respiratory pathogens such as Mtb is a balance between the activity of inflammation-inducing scavenger cells seeking to destroy such pathogens, and innate immunosuppressive activity seeking to minimize inflammatory damage to the delicate alveoli which could compromise gas exchange and lung function [31][32][33][34]. Pulmonary surfactant, a surface-active lipoprotein complex secreted by Type II alveolar cells to reduce surface tension in the alveoli and prevent their collapse during expiration, also may act as an immunosuppressant.…”

Section: Potential Role Of Mucosal Humoral Responses In Contributing mentioning

confidence: 99%

Developing aerosol vaccines for Mycobacterium tuberculosis: Workshop proceedings

Achkar¹,

Beverley²,

Boom³

et al. 2015

Vaccine

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On April 9, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "Developing Aerosol Vaccines for Mycobacterium tuberculosis" in Bethesda, MD. The purpose of the meeting was to explore the potential for developing aerosol vaccines capable of preventing infection with M. tuberculosis (Mtb), preventing the development of active tuberculosis (TB) among those latently infected with Mtb, or as immunotherapy for persons with active TB. The workshop was organized around four key questions relevant to developing and assessing aerosol TB vaccines: (1) What is the current knowledge about lung immune responses and early pathogenesis resulting after Mtb infection and what are the implications for aerosol TB vaccine strategies? (2) What are the technical issues surrounding aerosol vaccine delivery? (3) What is the current experience in aerosol TB vaccine development? and (4) What are the regulatory implications of developing aerosol vaccines, including those for TB? Lessons learned from the WHO effort to develop an aerosol measles vaccine served as a case example for overall discussions at the meeting. Workshop participants agreed that aerosol delivery represents a potentially important strategy in advancing TB vaccine development efforts. As no major regulatory, manufacturing or clinical impediments were identified, members of the workshop emphasized the need for greater support to further explore the potential for this delivery methodology, either alone or as an adjunct to traditional parenteral methods of vaccine administration.

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Modeling the immune rheostat of macrophages in the lung in response to infection

Cited by 29 publications

References 0 publications

Mathematical model of sarcoidosis

Mathematical model of sarcoidosis

Macrophage polarization in pathology

Developing aerosol vaccines for Mycobacterium tuberculosis: Workshop proceedings

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