A compendium of molecules involved in vector-pathogen interactions pertaining to malaria

Sreenivasamurthy, Sreelakshmi K.; Dey, Gourav; Manjula, R; Kumar, Manish; Gupta, Manoj Kumar; Mohanty, Ajeet Kumar; Harsha, Hc; Sharma, Pushkar; Kumar, Nirbhay; Pandey, Akhilesh; Kumar, Ashwani; Prasad, T. S. Keshava

doi:10.1186/1475-2875-12-216

Cited by 42 publications

(37 citation statements)

References 43 publications

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“…To date, a number of components of the mosquito innate immune response have been described that modulate Plasmodium development (1,27,28), yet our understanding of the mechanisms that limit Plasmodium development remains limited. Importantly, most studies have evaluated Plasmodium oocyst numbers at a single endpoint, thus missing the mechanistic detail of the early and late responses that play distinct roles in defending the mosquito from parasite infection.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Sporozoites must also travel in the mosquito, and this journey also often suffers from similar confusion between active migration and passive transport [42][43][44]. Sporozoites develop in oocysts in the mosquito midgut wall, and must exit into the hemocoel and go to the salivary gland.…”

Section: Sporozoite Movements In the Mosquitomentioning

confidence: 99%

Active migration and passive transport of malaria parasites

Douglas

Amino

Sinnis

et al. 2015

Trends in Parasitology

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“…In these mosquitoes numerous anti-bacterial and/or -plasmodial immune molecules have been identified, which effectively kill Plasmodium at different stages of development [10][11][12][13][14][15][16][17]. Some of these immune molecules successfully control the growth of Plasmodium berghei (mouse malaria) however, they are incompetent to regulate P. falciparum (human malaria) development [18,19].…”

Section: Introductionmentioning

confidence: 99%

Identification of an Anopheles Lineage-Specific Unique Heme Peroxidase HPX15: A Plausible Candidate for Arresting Malaria Parasite Development

Kajla

Gupta²,

Kakani³

et al. 2015

J Phylogenetics Evol Biol

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Background: Human malaria parasite Plasmodium falciparum is transmitted by several species of Anopheles mosquito. The advancement of drug-resistant parasites and insecticide resistance in mosquito vectors are major hurdles in the malaria control. Alternatively, the manipulation of mosquito immunity is also an ideal way to block Plasmodium development inside the insect host. This approach demands the identification of key mosquito molecules that regulate anti-plasmodial immunity. Our previous findings revealed that the silencing of Anopheles gambiae heme peroxidase 15 (AgHPX15, AGAP013327) induced mosquito innate immunity and drastically suppressed the development of human and rodent malaria parasites. Further, we aim to characterize HPX15 orthologs in Indian malaria vectors and other worldwide-distributed anophelines to understand the novelty of this molecule as a plausible target to block Plasmodium development.

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A compendium of molecules involved in vector-pathogen interactions pertaining to malaria

Cited by 42 publications

References 43 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

Active migration and passive transport of malaria parasites

Identification of an Anopheles Lineage-Specific Unique Heme Peroxidase HPX15: A Plausible Candidate for Arresting Malaria Parasite Development

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