AP-1/Fos-TGase2 Axis Mediates Wounding-induced Plasmodium falciparum Killing in Anopheles gambiae

Nsango, Sandrine E.; Pompon, Julien; Xie, Ting; Rademacher, Annika; Fraiture, Malou; Thoma, Martine; Awono-Ambene, Parfait; Moyou, Roger Somo; Morlais, Isabelle; Levashina, Elena A.

doi:10.1074/jbc.m112.443267

Cited by 24 publications

(35 citation statements)

References 62 publications

(63 reference statements)

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“…Similar to the suggested role of hemocytes in Drosophila (33, 34), mosquito hemocyte differentiation may promote a wound-healing response that in turn negatively influences parasite survival. In support of this hypothesis, genes involved in wound healing have been implicated in P. falciparum killing (35). Alternatively, we cannot exclude that oocyst recognition may itself trigger hemocyte differentiation.…”

Section: Discussionmentioning

confidence: 79%

Hemocyte differentiation mediates the mosquito late-phase immune response against Plasmodium in Anopheles gambiae

Smith

Barillas‐Mury

Jacobs-Lorena

2015

Proc. Natl. Acad. Sci. U.S.A.

143

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Plasmodium parasites must complete development in the mosquito vector for transmission to occur. The mosquito innate immune response is remarkably efficient in limiting parasite numbers. Previous work has identified a LPS-induced TNFα transcription factor (LITAF)-like transcription factor, LITAF-like 3 (LL3), which significantly influences parasite numbers. Here, we demonstrate that LL3 does not influence invasion of the mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune response that decreases oocyst survival. LL3 expression in the midgut and hemocytes is activated by ookinete midgut invasion and is independent of the mosquito microbiota, suggesting that LL3 may be a component of a wound-healing response. LL3 silencing abrogates the ability of mosquito hemocytes to differentiate and respond to parasite infection, implicating hemocytes as critical modulators of the late-phase immune response.osquitoes of the genus Anopheles are the obligate vectors for the transmission of the malaria parasite. Despite much effort invested to understand the interactions between the mosquito immune system and the parasite, our knowledge of these processes remains incomplete. The mosquito innate immune response effectively reduces parasite numbers, resulting in a severe bottleneck at the oocyst stage (1). There is evidence to suggest that multiple pathways contribute to parasite killing during two separate stages, or phases, of parasite development (1). An "early phase" occurs ∼18-24 h after blood feeding, as Plasmodium ookinetes invade the midgut epithelium and emerge on the basal side facing the hemocoel. During invasion, ookinetes are marked by epithelial nitration in a response regulated by the Jun N-terminal kinase (JNK) pathway, to promote thioester-containing protein 1 (TEP1) binding to the ookinete surface (2, 3). Once bound, TEP1 is believed to initiate a complement-like cascade that ultimately leads to parasite lysis or melanization (4-7).Parasites that evade this early-phase complement-like recognition and elimination are thought to be subjected to a second, "latephase" immune response that further decreases parasite numbers. This model is supported by the observation that the number of mature oocysts is significantly less than the number of early oocysts (8). Silencing the transcription factors STAT-A and STAT-B significantly increases oocyst survival, thus implicating the STAT pathway in this response (8). Conversely, constitutive activation of the STAT pathway via silencing the repressor SOCS (suppressor of cytokine signaling) resulted in increased levels of nitric oxide synthase (NOS) production and enhanced oocyst killing (8). These observations are in agreement with other studies that implicate NOS and subsequent NO production as important determinants of malaria parasite survival (9-11).Previously, we have characterized a LITAF-like transcription factor, LPS-induced TNFα transcription factor (LITAF)-like 3 (LL3), in Anopheles gambiae that mediates a potent antiPlasmod...

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Section: Discussionmentioning

confidence: 79%

Hemocyte differentiation mediates the mosquito late-phase immune response against Plasmodium in Anopheles gambiae

Smith

Barillas‐Mury

Jacobs-Lorena

2015

Proc. Natl. Acad. Sci. U.S.A.

143

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“…Recently AP-1 was demonstrated to be a key mediator of anti-plasmodial immunity in An. gambiae (Garver et al, 2013;Nsango et al, 2013). Our results show that the binding efficiency of the AP-1 motif of As-pro-PO V with the nuclear extract of Ar.…”

Section: Discussionmentioning

confidence: 67%

The dual roles of Armigeres subalbatus prophenoloxidase V in parasite melanization and egg chorion melanization in the mosquito Ar. subalbatus

Tsao¹,

Chen²,

Li³

et al. 2015

Insect Biochemistry and Molecular Biology

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“…This is not surprising given that the JNK pathway is a well-known regulator of wounding responses in Drosophila [12] and midgut invasion by ookinetes entails considerable damage to midgut cells [13]. Consistently, other studies revealed a link between wounding and antiparasitic responses [14][15][16][17]. Indeed, within the first 3 h after wounding, the wounding-responsive AP1 factor Fos induces expression of a group of genes involved in wound healing, including the transglutaminase 2 (TGase2).…”

Section: Cellular and Molecular Responses To Plasmodium Infectionmentioning

confidence: 72%

“…TGase 2 has been associated with coagulation, and it stimulates P. falciparum killing in An. gambiae [16]. The mechanisms of tissue-specific wounding responses remain unclear in An.…”

Section: Cellular and Molecular Responses To Plasmodium Infectionmentioning

confidence: 99%

Mosquito defenses against Plasmodium parasites

Severo

Levashina

2014

Current Opinion in Insect Science

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AP-1/Fos-TGase2 Axis Mediates Wounding-induced Plasmodium falciparum Killing in Anopheles gambiae

Cited by 24 publications

References 62 publications

Hemocyte differentiation mediates the mosquito late-phase immune response against Plasmodium in Anopheles gambiae

Hemocyte differentiation mediates the mosquito late-phase immune response against Plasmodium in Anopheles gambiae

The dual roles of Armigeres subalbatus prophenoloxidase V in parasite melanization and egg chorion melanization in the mosquito Ar. subalbatus

Mosquito defenses against Plasmodium parasites

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