Fever-Induced Heat Shock Protein-70 Regulates Macrophage IL-1β and IL-10 Secretion During Mycobacterium tuberculosis...

Area of Science:

• Immunology
• Infectious Diseases
• Molecular Biology

Background:

• Fever is a common symptom in tuberculosis (TB) patients.
• Heat-shock proteins (HSPs), like HSP70, are involved in protein folding and immune modulation.
• The mechanisms by which fever affects immune responses in TB are not fully understood.

Purpose of the Study:

• To investigate the impact of fever on Mycobacterium tuberculosis (Mtb)-induced macrophage inflammatory responses.
• To elucidate the specific role of HSP70 in these fever-modulated immune responses.

Main Methods:

• Human monocyte-derived macrophages (MDM) were infected with Mtb at normal (37°C) and febrile (40°C) temperatures.
• Gene expression and secretion of cytokines (IL-1β, IL-10) were measured.
• HSP70 secretion, intracellular accumulation, and functional antagonism were analyzed.
• Macrophage and HSP70 presence in TB patient granulomas was examined.

Main Results:

• Fever (40°C) suppressed Mtb-induced IL-1β and IL-10 gene expression and secretion from MDM.
• Fever enhanced Mtb-induced HSP70 secretion and intracellular accumulation.
• Extracellular HSP70 and HSP70-expressing macrophages were found in TB granulomas.
• HSP70 antagonism reduced IL-1β secretion during fever, but not IL-10.
• Recombinant HSP70 increased IL-1β secretion at normal temperatures.
• Extracellular HSP70 negatively regulated its own secretion.

Conclusions:

• Fever and HSP70 expression significantly modulate the innate immune response to Mtb infection.
• HSP70 plays a complex role in regulating pro-inflammatory cytokine production during TB.
• These findings suggest potential therapeutic strategies targeting host responses in TB.