Annexin1 regulates DC efferocytosis and cross-presentation during Mycobacterium tuberculosis infection
Fanny Tzelepis, … , Luis Bruno Barreiro, Maziar Divangahi
Fanny Tzelepis, … , Luis Bruno Barreiro, Maziar Divangahi
Published December 22, 2014
Citation Information: J Clin Invest. 2015;125(2):752-768. https://doi.org/10.1172/JCI77014.
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Research Article Infectious disease

Annexin1 regulates DC efferocytosis and cross-presentation during Mycobacterium tuberculosis infection

Abstract

The phagocytosis of apoptotic cells and associated vesicles (efferocytosis) by DCs is an important mechanism for both self tolerance and host defense. Although some of the engulfment ligands involved in efferocytosis have been identified and studied in vitro, the contributions of these ligands in vivo remain ill defined. Here, we determined that during Mycobacterium tuberculosis (Mtb) infection, the engulfment ligand annexin1 is an important mediator in DC cross-presentation that increases efferocytosis in DCs and intrinsically enhances the capacity of the DC antigen–presenting machinery. Annexin1-deficient mice were highly susceptible to Mtb infection and showed an impaired Mtb antigen–specific CD8+ T cell response. Importantly, annexin1 expression was greatly downregulated in Mtb-infected human blood monocyte–derived DCs, indicating that reduction of annexin1 is a critical mechanism for immune evasion by Mtb. Collectively, these data indicate that annexin1 is essential in immunity to Mtb infection and mediates the power of DC efferocytosis and cross-presentation.

Authors

Fanny Tzelepis, Mark Verway, Jamal Daoud, Joshua Gillard, Kimya Hassani-Ardakani, Jonathan Dunn, Jeffrey Downey, Marilena Elena Gentile, Joanna Jaworska, Anthony Michel Jean Sanchez, Yohann Nédélec, Hojatollah Vali, Maryam Tabrizian, Arnold Scott Kristof, Irah Luther King, Luis Bruno Barreiro, Maziar Divangahi

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Figure 1

Anxa1–/– mice are highly susceptible to Mtb infection.

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Anxa1–/– mice are highly susceptible to Mtb infection. (A and B) Surviva...
(A and B) Survival of WT and Anxa1–/– mice (n = 9–10/group) infected i.v. with approximately 108 (A) or approximately 106 (B) virulent Mtb bacilli. (C) Lung tissues from WT (upper panel) and Anxa1–/– (lower panel) mice stained with Ziehl–Neelsen for detection of Mtb bacilli after 20 days infection (i.v.) with approximately 108 virulent Mtb. Original magnification, ×40. (D) Bacterial burden in the lungs after 14, 35, and 90 days of aerosol infection with Mtb (n = 5/group). (E) Survival of WT and Anxa1–/– mice (n = 7/group) after aerosol infection with virulent Mtb. *P < 0.05 (1-way ANOVA). Survival data were analyzed by log-rank test.