The SecA2 secretion factor of Mycobacterium tuberculosis promotes growth in macrophages and inhibits the host immune response
| Autor: | Karen P. McKinnon, Miriam Braunstein, Sherry Kurtz, Jenny P.-Y. Ting, Marschall S. Runge |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Phagocyte
medicine.medical_treatment Immunology Nitric Oxide Synthase Type II Microbiology Mycobacterium tuberculosis chemistry.chemical_compound Mice Immune system Bacterial Proteins medicine Immune Tolerance Macrophage Animals Secretion Tuberculosis Pulmonary Reactive nitrogen species Adenosine Triphosphatases Aerosols Cellular Microbiology: Pathogen-Host Cell Molecular Interactions biology Growth factor Macrophages Membrane Transport Proteins Macrophage Activation biology.organism_classification Reactive Nitrogen Species Mice Mutant Strains Infectious Diseases medicine.anatomical_structure Phenotype chemistry Cytokines Parasitology Tumor necrosis factor alpha Female Reactive Oxygen Species Gene Deletion |
| Zdroj: | Infection and immunity. 74(12) |
| ISSN: | 0019-9567 |
| Popis: | The SecA protein is present in all bacteria, and it is a central component of the general Sec-dependent protein export pathway. An unusual property ofMycobacterium tuberculosisis the presence of two SecA proteins: SecA1, the essential “housekeeping” SecA, and SecA2, the accessory secretion factor. Here, we report that a ΔsecA2mutant ofM. tuberculosiswas defective for growth in the early stages of low-dose aerosol infection of C57BL/6 mice, a time during which the bacillus is primarily replicating in macrophages. Consistent with this in vivo phenotype, we found that the ΔsecA2mutant was defective for growth in macrophages from C57BL/6 mice. The ΔsecA2mutant was also attenuated for growth in macrophages from phox−/−mice and from NOS2−/−mice. These mice are defective in the reactive oxygen intermediate (ROI)-generating phagocyte oxidase and the reactive nitrogen intermediate (RNI)-generating inducible nitric oxide synthase, respectively. This indicated a role for SecA2 in the intracellular growth ofM. tuberculosisthat is independent of protecting against these ROIs or RNIs. Macrophages infected with the ΔsecA2mutant produced higher levels of tumor necrosis factor alpha, interleukin-6, RNI, and gamma interferon-induced major histocompatibility complex class II. This demonstrated a function forM. tuberculosisSecA2 in suppressing macrophage immune responses, which could explain the role of SecA2 in intracellular growth. Our results provide another example of a relationship betweenM. tuberculosisvirulence and inhibition of the host immune response. |
| Databáze: | OpenAIRE |
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