Macrophage reprogramming by mycolic acid promotes a tolerogenic response in experimental asthma.

Rationale: Mycolic acid (MA) constitutes a major and distinguishing cell wall biolipid from Mycobacterium tuberculosis. MA interferes with the lipid homeostasis of alveolar macrophages, inducing differentiation into foamy macrophages exhibiting increased proinflammatory function.

Objectives: We verified the interference of this altered macrophage function with inhaled antigen-triggered allergic airway inflammation and underlying Th2 lymphocyte reactivity.

Airway IgG counteracts specific and bystander allergen-triggered pulmonary inflammation by a mechanism dependent on Fc gamma R and IFN-gamma.

Besides IgE, the Ab isotype that gives rise to sensitization and allergic asthma, the immune response to common inhalant allergens also includes IgG. Increased serum titers of allergen-specific IgG, induced spontaneously or by allergen vaccination, have been implicated in protection against asthma. To verify the interference of topical IgG with the allergen-triggered eosinophilic airway inflammation that underlies asthma, sensitized mice were treated by intranasal instillation of specific IgG, followed by allergen challenge.

Antigen presentation by local macrophages promotes nonallergic airway responses in sensitized mice.

Local inflammatory responses involve relocating immune functions generated by previous immunization to confined parts of the body, and hence are presumed to reflect the prevailing systemic immune bias. To verify to what extent local antigen-presenting cells (APCs) may modulate immune inflammation, we analyzed the consequences of antigen presentation by macrophages on Th2-dependent airway inflammation in ovalbumin (OVA)-sensitized mice. In contrast to challenge with free OVA, which triggers airway eosinophilia and Th2 cell recruitment, intratracheal instillation of immortalized spleen macrophages (Mf4/4 cells), pulsed with OVA, promoted a nonallergic airway response featuring recruitment of interferon-gamma-producing Th1 cells.