The Arabidopsis Tandem Zinc Finger 9 Protein Binds RNA and Mediates Pathogen-Associated Molecular Pattern-Triggered Immune Responses

ABSTRACTThere is a constant need for improved adjuvants to augment the induction of immune responses against tumor-associated antigens (TAA) during immunotherapy. Previous studies have established that listeriolysin O (LLO), a cholesterol-dependent cytolysin derived fromListeria monocytogenes, exhibits multifaceted effects to boost the stimulation of immune responses to a variety of antigens. However, the direct ability of LLO as an adjuvant and whether it acts as a pathogen-associated molecular pattern (PAMP) have not been demonstrated. In this paper, we show that a detoxified, nonhemolytic form of LLO (dtLLO) is an effective adjuvant in tumor immunotherapy and may activate innate and cellular immune responses by acting as a PAMP. Our investigation of the adjuvant activity demonstrates that dtLLO, either fused to or administered as a mixture with a human papillomavirus type 16 (HPV-16) E7 recombinant protein, can augment antitumor immune responses and facilitate tumor eradication. Further mechanistic studies using bone marrow-derived dendritic cells suggest that dtLLO acts as a PAMP by stimulating production of proinflammatory cytokines and inducing maturation of antigen-presenting cells (APC). We propose that dtLLO is an effective adjuvant for tumor immunotherapy, and likely for other therapeutic settings.

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CD2-1, the C-Terminal Region of Flagellin, Modulates the Induction of Immune Responses in Rice

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-11-14-0372-r ◽

2015 ◽

Vol 28 (6) ◽

pp. 648-658 ◽

Cited By ~ 20

Author(s):

Yuya Katsuragi ◽

Ryota Takai ◽

Takehito Furukawa ◽

Hiroyuki Hirai ◽

Takumi Morimoto ◽

...

Keyword(s):

Immune Responses ◽

Pathogenic Bacteria ◽

Terminal Region ◽

Recognition Mechanism ◽

Epitope Recognition ◽

Molecular Pattern ◽

Pathogen Associated Molecular Pattern ◽

Rice Ortholog

Flagellin from the rice avirulent N1141 strain of Acidovorax avenae functions as a pathogen-associated molecular pattern (PAMP) and induces PAMP-triggered immunity (PTI) in rice. To study the recognition mechanism of flagellin in rice, we attempted to define one or more regions of the flagellin protein required to activate the PTI response. Based on domain classification, we produced four fragments of N1141 flagellin: N-terminal D0, D1. and D2 domains (ND0-2), N-terminal D2, D3, and C-terminal D2 domains (ND2-CD2), C-terminal D2, D1, and D0 domains (CD2-0), and C-terminal D2 and D1 domains (CD2-1). The C-terminal CD2-1 and CD2-0 fragments induced PTI responses in cultured rice cells. Synthetic flg22, which is sufficient to produce the flagellin response in Arabidopsis, and the N-terminal flagellin fragments containing flg22 region elicited very weak immune responses in rice. OsFLS2, the rice ortholog of AtFLS2, which mediates flg22 recognition, was not involved in CD2-0 or CD2-1 recognition in rice. In addition, CD2-0 triggered resistance to coinfection with pathogenic bacteria. Taken together, these data suggest that rice mainly recognizes flagellin CD2-1 by a receptor distinct from OsFLS2 and that this epitope recognition leads to PTI responses.

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