scholarly journals Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key theory

2015 ◽  
Vol 112 (49) ◽  
pp. 15178-15183 ◽  
Author(s):  
Alvaro Molina-Cruz ◽  
Gaspar E. Canepa ◽  
Nitin Kamath ◽  
Noelle V. Pavlovic ◽  
Jianbing Mu ◽  
...  
Keyword(s):  
Immune System ◽  
Malaria Transmission ◽  
Immune Evasion ◽  
Mosquito Species ◽  
Haplotype Diversity ◽  
Malaria Vectors ◽  
Selective Force ◽  
Genetic Traits ◽  
Geographic Population

Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the “lock-and-key theory” of P. falciparum globalization, is proposed, and its implications are discussed.

Immunotherapy: New insights in breast cancer treatment

2021 ◽  
pp. 1-10
Author(s):  
Bader Alshehri
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Treatment ◽  
Immune Evasion ◽  
Breast Tumor ◽  
Parp Inhibitor ◽  
Breast Cancer Treatment ◽  
New Treatment

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.

scholarly journals The Multifaceted Role of Macrophages in Oncolytic Virotherapy

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1570
Author(s):  
Laura Hofman ◽  
Sean E. Lawler ◽  
Martine L. M. Lamfers
Keyword(s):  
Immune System ◽  
Immune Evasion ◽  
Tumour Microenvironment ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Comprehensive Overview ◽  
Central Function ◽  
Cancer Hallmarks ◽  
Viral Spread

One of the cancer hallmarks is immune evasion mediated by the tumour microenvironment (TME). Oncolytic virotherapy is a form of immunotherapy based on the application of oncolytic viruses (OVs) that selectively replicate in and induce the death of tumour cells. Virotherapy confers reciprocal interaction with the host’s immune system. The aim of this review is to explore the role of macrophage-mediated responses in oncolytic virotherapy efficacy. The approach was to study current scientific literature in this field in order to give a comprehensive overview of the interactions of OVs and macrophages and their effects on the TME. The innate immune system has a central influence on the TME; tumour-associated macrophages (TAMs) generally have immunosuppressive, tumour-supportive properties. In the context of oncolytic virotherapy, macrophages were initially thought to predominantly contribute to anti-viral responses, impeding viral spread. However, macrophages have now also been found to mediate transport of OV particles and, after TME infiltration, to be subjected to a phenotypic shift that renders them pro-inflammatory and tumour-suppressive. These TAMs can present tumour antigens leading to a systemic, durable, adaptive anti-tumour immune response. After phagocytosis, they can recirculate carrying tissue-derived proteins, which potentially enables the monitoring of OV replication in the TME. Their role in therapeutic efficacy is therefore multifaceted, but based on research applying relevant, immunocompetent tumour models, macrophages are considered to have a central function in anti-cancer activity. These novel insights hold important clinical implications. When optimised, oncolytic virotherapy, mediating multifactorial inhibition of cancer immune evasion, could contribute to improved patient survival.

scholarly journals Molecular Characterization and Genotype Distribution of Thioester-containing Protein 1 Gene, A Key Regulator of Malaria Transmission in An. Gambiae Mosquitoes in Western Kenya

2021 ◽  
Author(s):  
Shirley A. Onyango ◽  
Kevin O. Ochwedo ◽  
Maxwell G. Machani ◽  
Collince J. Omondi ◽  
Isaiah Debrah ◽  
...  
Keyword(s):  
Population Structure ◽  
Anopheles Gambiae ◽  
Malaria Transmission ◽  
Mosquito Species ◽  
Malaria Vectors ◽  
Fixation Index ◽  
Genotype Distribution ◽  
Low Frequencies ◽  
Western Kenya ◽  
Significant Difference

Abstract BackgroundEvolutionary pressures lead to the selection of efficient malaria vectors either resistant or susceptible to Plasmodiumparasites.These forcesmay elevate the introduction of new species genotypes that adapt to new breeding habitats which could have serious implications on malaria transmission.Thioester-containing protein 1 (TEP1) of Anopheles gambiaeplays an important role in innate immune defenses against parasites. This study aims to characterize the distribution pattern of TEP1 polymorphisms determining vector competence and subsequently malaria transmission in western Kenya. MethodsAnopheles gambiaeadult and larvae were collected using pyrethrum spray catches (PSC) and plastic dippers respectivelyfrom Homa Bay, Kakamega, Bungoma, and Kisumu countiesbetween 2017 and 2020.Collected adults and larvae reared to the adult stage were morphologically identified and then identified to sibling species by PCR.TEP1 alleles were determined using restriction fragment length polymorphisms-polymerase chain reaction (RFLP-PCR) and to validate the TEP1 genotyping results, a representative sample of alleles was sequenced.ResultsTwo TEP1 alleles (TEP1*S1 and TEP1*R2)and three corresponding genotypes (*S1/S1, *R2/S1, and *R2/R2)were identified. TEP1*S1 and TEP1*R2 with their corresponding genotypes, homozygous *S1/S1 and heterozygous *R2/S1 were widely distributed across all sites with allele frequencies of approximately 80% and 20%, respectively bothin An. gambiaeand An. arabiensis. There was no significant difference detected among the population and between the two mosquito species in TEP1 allele frequency and genotype frequency. The overall low levels in population structure (FST= 0.019) across all sites corresponded to an effective migration index (Nm= 12.571) and lowNei’s genetic distance values (<0.500) among the subpopulation.The comparative fixation index values revealed minimal genetic differentiation between speciesand high levels of gene flow among populations.ConclusionThere is a low genetic diversity and population structure in western Kenya. TEP1* R2 and TEP1*S1 were the most common alleles in both species which may have been maintained through generations in time, However, the TEP1*R2 allele was in low frequencies and may be used to estimatemalaria prevalence. Continued surveillance of the distribution of TEP1 is essential for monitoring the population dynamics of local vectors and their implications on malaria transmission and hence designing targeted vector interventions.

scholarly journals Molecular Identification of Native Wolbachia Pipientis in Anopheles Minimus in a Low-Malaria Transmission Area of Umphang Valley Along the Thailand-Myanmar Border

2020 ◽  
Author(s):  
Nongnat Tongkrajang ◽  
Pichet Ruenchit ◽  
Chatchai Tananchai ◽  
Theeraphap Chareonviriyaphap ◽  
Kasem Kulkeaw
Keyword(s):  
Malaria Transmission ◽  
Dna Sequences ◽  
Phylogenetic Trees ◽  
Mosquito Species ◽  
Malaria Vectors ◽  
Molecular Evidence ◽  
Wolbachia Pipientis ◽  
Close Relationship ◽  
Transmission Area ◽  
Low Malaria Transmission

Abstract BackgroundWolbachia, obligate intracellular bacteria, infect the majority of arthropods, including many mosquito species of medical importance. Some Wolbachia strains interfere with the development of Plasmodium parasites in female Anopheles, a major vector of malaria. The use of Wolbachia as a means to block malaria transmission is an emerging vector control strategy in highly endemic areas. Hence, identification of native Wolbachia strains in areas where malaria transmission is low may uncover a particular Wolbachia strain capable of Plasmodium interference. This study aims to identify native Wolbachia strains in female Anopheles spp. that are predominant in a low-malaria transmission area in mainland Southeast Asia.MethodsFollowing a two-year survey of malaria vectors in Umphang Valley of Tak Province, Thailand, DNA extracts of female An. minimus, An. peditaeniatus, An. maculatus, and An. dirus were subjected to amplification of the conserved region of the 16S rRNA-encoding gene. The DNA sequences of the amplicons were phylogenetically compared with those of known Wolbachia strains.ResultsAmong four Anopheles spp., amplification was detected in only the DNA samples from An. minimus. The DNA sequencing of amplicons revealed 100% similarity to Wolbachia pipientis, confirming the specificity of amplification. The phylogenetic trees indicate a close relationship with Wolbachia strains in subgroup B.ConclusionTo the best of our knowledge, the data presented herein provide the first molecular evidence of a Wolbachia strain in An. minimus, hereinafter named wAnmi, in a low-malaria transmission area in the Umphang Valley of western Thailand. Further biological characterization is required to examine its potential for malaria transmission control in the field.

scholarly journals Current and emerging immunotherapeutic approaches to the treatment of multiple myeloma

2019 ◽  
Vol 10 ◽  
pp. 204062071985417
Author(s):  
Dawn Swan ◽  
Kevin Lynch ◽  
Mark Gurney ◽  
Michael O’Dwyer
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Immune Evasion ◽  
Proteasome Inhibitors ◽  
Standard Of Care ◽  
Bispecific Antibodies ◽  
Clinical Use ◽  
Immunomodulatory Drugs ◽  
Care Regimes

Multiple myeloma (MM) has a worldwide incidence of 1–5/100,000/year. Outcomes have improved significantly in recent years following incorporation of immunomodulatory drugs and proteasome inhibitors into standard-of-care regimes. MM is profoundly immunosuppressive, enabling immune evasion, proliferation and disease progression. The role of the immune system in MM is becoming increasingly characterized and understood, and numerous therapies are under development or in routine clinical use targeting these elements of MM pathogenesis. In this review we discuss the immunosuppressive effects of MM, then the therapies targeting these defects. Specifically, we review the monoclonal and bispecific antibodies, alongside adoptive cellular therapies currently under investigation.

Role of the surface coat of Romanomermis culicivorax in immune evasion

Nematology ◽  
2007 ◽  
Vol 9 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Edward Platzer ◽  
Randy Gaugler ◽  
Muhammad Shamseldean
Keyword(s):  
Immune System ◽  
Immune Evasion ◽  
Immune Reaction ◽  
Parasitic Nematodes ◽  
Broad Host Range ◽  
Host Immune System ◽  
Surface Coat ◽  
Mermithid Nematode ◽  
Host Parasite

AbstractInteractions of the mermithid nematode Romanomermis culicivorax with the immune system of mosquito larvae were examined by scanning electron microscopy. The host immune system rapidly recognised invading parasites, as granulocytes and discharged granules were observed attached to parasitic nematodes within 5 min. Melanin deposition was infrequently observed. As a counter measure, the parasites secreted and shed an extracellular surface coat which aided immune evasion. During the first 4 days of infection, when parasite growth was limited, the coat served as a disposable, renewable barrier between parasite and host that was intermittently shed to cleanse the nematode of adhering host immune products. In the later infection phase the parasite grew rapidly and was beyond the effect of the depleted host immune response. The broad host range of R. culcivorax within culicines may be partly a function of the nonspecific defence it mounts against the host immune system. In summary, shedding of the surface coat is an adaptive counter response by R. culicivorax to the mosquito immune reaction to infection and provides a classic example of host-parasite coevolution.

scholarly journals Plasmodium Infections in Anopheles Mosquitoes in Ubon Ratchathani Province, Northeastern Thailand During a Malaria Outbreak

2018 ◽  
Vol 34 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Anchana Sumarnrote ◽  
Vincent Corbel ◽  
Hans J. Overgaard ◽  
Olivier Celhay ◽  
Nattapol Marasri ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Malaria Vectors ◽  
Anopheles Species ◽  
Community Activities ◽  
Anopheles Mosquitoes ◽  
Human Landing ◽  
Suitable Habitats ◽  
Malaria Outbreak ◽  
Northeastern Thailand

ABSTRACT An unprecedented malaria outbreak occurred in Ubon Ratchathani Province, northeastern Thailand, in 2014. The province showed the highest number of malaria cases of all Thai provinces. Five entomological surveys were conducted at 8 sentinel sites from September 2013 to September 2015 to address the role of different Anopheles species in malaria transmission. Mosquito collections were conducted using human landing catches and cow bait. A total of 10,369 Anopheles mosquitoes were collected and 2,240 were morphologically identified as potential malaria vectors, including An. dirus (n = 78), An. minimus (n = 18), An. sawadwongporni (n = 4), An. barbirostris s.l. (n = 819), An. philippinensis (n = 612), An. nivipes (n = 676), An. annularis (n = 42), An. aconitus (n = 7), and An. rampae (n = 142). Real-time polymerase chain reaction was used to screen for the presence of Plasmodium spp. in salivary glands. The proportion of primary vectors of surveyed villages was very low (&lt;1%), and no Plasmodium-infected specimens were detected among in the 2,240 Anopheles mosquitoes tested. The absence of positive Plasmodium samples during malaria outbreaks suggests that malaria transmission most likely occurred outside the villages, particularly in the deep-forested hilly areas that provided suitable habitats for competent malaria vectors. These results emphasize the need to develop vector control related to village community activities to reduce malaria transmission along Thailand border areas.

scholarly journals Acetylation in Tumor Immune Evasion Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Lu ◽  
Xiang He ◽  
Lijuan Zhang ◽  
Ran Zhang ◽  
Wenzheng Li
Keyword(s):  
Immune System ◽  
Tumor Immunity ◽  
Immune Evasion ◽  
Tumor Suppressors ◽  
Pathological Process ◽  
System Function ◽  
Comprehensive Understanding ◽  
Tumor Immune Evasion ◽  
Immune System Function

Acetylation is considered as one of the most common types of epigenetic modifications, and aberrant histone acetylation modifications are associated with the pathological process of cancer through the regulation of oncogenes and tumor suppressors. Recent studies have shown that immune system function and tumor immunity can also be affected by acetylation modifications. A comprehensive understanding of the role of acetylation function in cancer is essential, which may help to develop new therapies to improve the prognosis of cancer patients. In this review, we mainly discussed the functions of acetylase and deacetylase in tumor, immune system and tumor immunity, and listed the information of drugs targeting these enzymes in tumor immunotherapy.

scholarly journals Bionomics and ecology of Anopheles merus along the East and Southern Africa coast

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Brian Bartilol ◽  
Irene Omedo ◽  
Charles Mbogo ◽  
Joseph Mwangangi ◽  
Martin K. Rono
Keyword(s):  
Malaria Transmission ◽  
Mosquito Species ◽  
Scale Up ◽  
Indoor Residual Spraying ◽  
Temporal Distribution ◽  
Malaria Vectors ◽  
Behavioural Plasticity ◽  
Insecticide Treated Nets ◽  
Resting Behaviour ◽  
Residual Malaria Transmission

AbstractMalaria transmission persists despite the scale-up of interventions such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS). Understanding the entomological drivers of transmission is key for the design of effective and sustainable tools to address the challenge. Recent research findings indicate a shift in vector populations from the notorious Anopheles gambiae (s.s.) as a dominant vector to other species as one of the factors contributing to the persistence of malaria transmission. However, there are gaps in the literature regarding the minor vector species which are increasingly taking a lead role in malaria transmission. Currently, minor malaria vectors have behavioural plasticity, which allows their evasion of vector control tools currently in use. To address this, we have reviewed the role of Anopheles merus, a saltwater mosquito species that is becoming an important vector of malaria transmission along the East and Southern African coast. We performed a literature review from PubMed and Google Scholar and reviewed over 50 publications relating to An. merus's bionomics, taxonomy, spatial-temporal distribution and role in malaria transmission. We found that An. merus is an important vector of malaria and that it contributes to residual malaria transmission because of its exophilic tendencies, insecticide resistance and densities that peak during the dry seasons as the freshwater mosquitoes decline. Spatial and temporal studies have also shown that this species has increased its geographical range, densities and vectorial capacity over time. In this review, we highlight the resting behaviour and breeding habitats of this mosquito, which could be targeted for surveillance studies and control interventions.

scholarly journals Molecular identification of native Wolbachia pipientis in Anopheles minimus in a low-malaria transmission area of Umphang Valley along the Thailand-Myanmar border

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Nongnat Tongkrajang ◽  
Pichet Ruenchit ◽  
Chatchai Tananchai ◽  
Theeraphap Chareonviriyaphap ◽  
Kasem Kulkeaw
Keyword(s):  
Malaria Transmission ◽  
Dna Sequences ◽  
Phylogenetic Trees ◽  
Mosquito Species ◽  
Malaria Vectors ◽  
Molecular Evidence ◽  
Wolbachia Pipientis ◽  
Close Relationship ◽  
Transmission Area ◽  
Low Malaria Transmission

Abstract Background Wolbachia, obligate intracellular bacteria, infect the majority of arthropods, including many mosquito species of medical importance. Some Wolbachia strains interfere with the development of Plasmodium parasites in female Anopheles, a major vector of malaria. The use of Wolbachia as a means to block malaria transmission is an emerging vector control strategy in highly endemic areas. Hence, identification of native Wolbachia strains in areas where malaria transmission is low may uncover a particular Wolbachia strain capable of Plasmodium interference. This study aims to identify native Wolbachia strains in female Anopheles spp. that are predominant in a low-malaria transmission area in mainland Southeast Asia. Methods Following a 2-year survey of malaria vectors in Umphang Valley of Tak Province, Thailand, DNA extracts of female An. minimus, An. peditaeniatus, and An. maculatus were subjected to amplification of the conserved region of the 16S rRNA-encoding gene. The DNA sequences of the amplicons were phylogenetically compared with those of known Wolbachia strains. Results Among three Anopheles spp., amplification was detected in only the DNA samples from An. minimus. The DNA sequencing of amplicons revealed 100% similarity to Wolbachia pipientis, confirming the specificity of amplification. The Wolbachia-positive An. minimus samples were devoid of Plasmodium 18S rRNA amplification. The phylogenetic trees indicate a close relationship with Wolbachia strains in subgroup B. Conclusion To the best of our knowledge, the data presented herein provide the first molecular evidence of a Wolbachia strain in An. minimus, hereinafter named wAnmi, in a low-malaria transmission area in the Umphang Valley of western Thailand. Further biological characterization is required to examine its potential for malaria transmission control in the field.

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