Antigen Presentation by Local Macrophages Promotes Nonallergic Airway Responses in Sensitized Mice

Gwenda Pynaert, Pieter Rottiers, Anuschka Haegeman, Sehra Sarita, Tom Van Belle, Johanna Korf, Johan Grooten

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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-γ-producing Th1 cells. Combining OVA-Mf4/4 instillation with OVA inhalation strongly reduced airway eosinophilia. Inflammation repression persisted after secondary OVA challenge and depended on the antigen-presenting ability of the macrophages. Arguing against Th1-mediated counter-regulation, Th1/Th2 ratios remained unaltered in macrophage-treated/OVA- challenged mice. In contrast, levels of interleukin-4 and interleukin-13 mRNA in lung tissue CD4+ T cells were strongly downregulated, indicating a suppression of Th2 cell activation. These results document a role for local macrophages/APCs in controlling the nature and intensity of local immune inflammatory responses. The resulting segregation of systemic and local levels of immune reactivity may enable local inflammation tolerance; it is a nonallergic airway response despite systemic sensitization.

Original languageEnglish (US)
Pages (from-to)634-641
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume29
Issue number5
DOIs
StatePublished - Nov 2003
Externally publishedYes

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Macrophages
Ovalbumin
Antigen Presentation
Antigens
Inflammation
Th2 Cells
Eosinophilia
Antigen-Presenting Cells
Immunization
Th1 Cells
T-cells
Interleukin-13
Human Body
Interleukin-4
Interferons
Inhalation
Down-Regulation
Spleen
Chemical activation
Tissue

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Antigen Presentation by Local Macrophages Promotes Nonallergic Airway Responses in Sensitized Mice. / Pynaert, Gwenda; Rottiers, Pieter; Haegeman, Anuschka; Sarita, Sehra; Van Belle, Tom; Korf, Johanna; Grooten, Johan.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 29, No. 5, 11.2003, p. 634-641.

Research output: Contribution to journalArticle

Pynaert, Gwenda ; Rottiers, Pieter ; Haegeman, Anuschka ; Sarita, Sehra ; Van Belle, Tom ; Korf, Johanna ; Grooten, Johan. / Antigen Presentation by Local Macrophages Promotes Nonallergic Airway Responses in Sensitized Mice. In: American Journal of Respiratory Cell and Molecular Biology. 2003 ; Vol. 29, No. 5. pp. 634-641.
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