TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: a next-generation two-compartmental model.
Tuberculosis (TB) is one of the earliest recorded human diseases and still one of the deadliest worldwide. Its causative agent is the bacteria Mycobacterium tuberculosis (Mtb). Cytokine-mediated macrophage activation is a necessary step in control of bacterial growth, and early immunologic events in lymph node and lung are crucial to the outcome of infection, although the factors that influence these environments and the immune response are poorly understood. Our goal is to build the next-generation two-compartmental model of the immune response to provide a gateway to more spatial and mechanistic investigations of M. tuberculosis infection in the LN and lung. Crucial immune factors emerge that affect macrophage populations and inflammation, namely TNF-dependent recruitment and apoptosis, and IL-10 levels. Surprisingly, bacterial load plays a less important role than TNF in increasing the population of infected macrophages and inflammation. Using a mathematical model, it is possible to distinguish the effects of pro-inflammatory (TNF) and anti-inflammatory (IL-10) cytokines on the spectrum of phagocyte populations (macrophages and dendritic cells) in the lung and lymph node. Our results suggest that TNF is a major mediator of recruitment of phagocytes to the lungs. In contrast, IL-10 plays a role in balancing the dominant macrophage phenotype in LN and lung.
Marino
Simeone
S
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA. simeonem@umich.edu
Myers
Amy
A
Flynn
JoAnne L
JL
Kirschner
Denise E
DE
D000818:Animals; D016764:Cell Polarity; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D056747:Immunomodulation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010586:Phagocytes / Q000166:cytology / Q000276:immunology*; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10