Murine Plasmodium chabaudi Malaria Increases Mucosal Immune Activation and the Expression of Putative HIV Susceptibility Markers in the Gut and Genital Mucosae

Chege, Duncan; Higgins, Sarah J.; McDonald, Chloë R.; Shahabi, Kamnoosh; Huibner, Sanja; Kain, Taylor; Kain, Dylan; Kim, Connie J.; Leung, Nelly; Amin, Mohsen; Geddes, Kaoru; Serghides, Lena; Philpott, Dana J.; Kimani, Joshua; Gray-Owen, Scott D.; Kain, Kevin C.; Kaul, Rupert

doi:10.1097/qai.0000000000000056

Cited by 6 publications

(5 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antibodies are known to play a key role in naturally acquired immunity to the blood stage of P. falciparum infection. Until a few years ago, most studies focused on understanding the role of IgG in the response to P. falciparum infection, with IgG1 and IgG3 considered to be the most protective ( 19 , 20 ); however, a role of IgM in malaria infection has also been considered more recently ( 21 ). We analyzed the presence of soluble Ig proteins using the Bio-Plex multiplex (Bio-Rad) system.…”

Section: Resultsmentioning

confidence: 99%

“…In early reports, purified IgG antibodies transferred from semi-immune adults to children acutely infected with P. falciparum reduced blood-stage parasitemia and disease severity ( 5 ). Subsequent studies identified key roles for immunoglobulins in anti-malaria immunity ( 19 , 20 , 25 ). Here, we found a significant variation of IgG1 and IgG3 in the supernatants of BAFF-var PBMCs without P. falciparum exposure as compared to BAFF-WT .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evolutionarily Selected Overexpression of the Cytokine BAFF Enhances Mucosal Immune Response Against P. falciparum

et al. 2020

View full text Add to dashboard Cite

We have previously shown that a variant of the TNFSF13B gene that we called BAFF-var increases the production of the cytokine BAFF, upregulating humoral immunity and increasing the risk for certain autoimmune diseases. In addition, genetic population signatures revealed that BAFF-var was evolutionarily advantageous, most likely by increasing resistance to malaria infection, which is a prime candidate for selective pressure. To evaluate whether the increased soluble BAFF (sBAFF) production confers protection, we experimentally assessed the role of BAFF-var in response to malaria antigens. Lysates of erythrocytes infected with Plasmodium falciparum (iRBCs) or left uninfected (uRBCs, control) were used to treat peripheral blood mononuclear cells (PBMCs) with distinct BAFF genotypes. The PBMCs purified from BAFF-var donors and treated with iRBCs showed different levels of specific cells, immunoglobulins, and cytokines as compared with BAFF-WT. In particular, a relevant differential effect on mucosal immunity B subpopulations have been observed. These findings point to specific immune cells and molecules through which the evolutionary selected BAFF-var may have improved fitness during P. falciparum infection.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evolutionarily Selected Overexpression of the Cytokine BAFF Enhances Mucosal Immune Response Against P. falciparum

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Infection by intestinal parasites upregulates activation markers in blood [78], and plasma inflammatory cytokines and blood CCR5 expression are increased in TB, both before therapy and during the early phases of treatment [79]. Whether this systemic inflammation causes immune changes in the genital (vaginal or penile) mucosa has not been studied in humans, but malaria in a mouse model was associated with substantial T cell immune activation in the genital and lower gastrointestinal tracts, and with increased CCR5 expression at both sites [80]. The short duration of many co-infections and their limited effect on the HIV plasma VL means that their effect on the epidemic may be relatively low if only the HIV-infected partner is considered [81], but this may be an underestimate since such models have not previously taken into account the possible effects of co-infections on susceptibility in the HIV-uninfected partner.…”

Section: Biological Factors That May Enhance Hiv Transmission In Sub-mentioning

confidence: 94%

Inflammation and HIV Transmission in Sub-Saharan Africa

et al. 2015

Self Cite

View full text Add to dashboard Cite

While the per-contact risk of sexual HIV transmission is relatively low, it is fourfold higher in sub-Saharan Africa, and this may partly explain the major global disparities that exist in HIV prevalence. Genital immune parameters are key determinants of HIV transmission risk, including epithelial integrity and the presence of highly HIV-susceptible intraepithelial or submucosal CD4+ T cell target cells. Biological parameters that may enhance mucosal HIV susceptibility in highly HIV-affected regions of sub-Saharan Africa include increased levels of mucosal inflammation, which can affect both epithelial integrity and target cell availability, as well as the increased mucosal surface area that is afforded by an intact foreskin, contraceptive choices, and intravaginal practices. There are multifactorial causes for increased mucosal inflammation, with the prevalence and nature of common co-infections being particularly relevant.

show abstract

“…In the 1980s-1990s, P. vivax was injected into patients with late-stage Lyme disease (Heimlich, 1990;Anonymous, 1991a, b) and into HIV-infected individuals. However, these practices were risky, P. vivax can be associated with the development of severe diseases with complications (Wassmer et al 2015) and their effectiveness was unproven (Chege et al 2014).…”

Section: A L a R I A A N O L D P U T A T Imentioning

confidence: 99%

Puzzling and ambivalent roles of malarial infections in cancer development and progression

Faure

2016

Parasitology

View full text Add to dashboard Cite

Scientific evidence strongly suggests that parasites are directly or indirectly associated with carcinogenesis in humans. However, studies have also indicated that parasites or their products might confer resistance to tumour growth. Plasmodium protozoa, the causative agents of malaria, exemplify the ambivalent link between parasites and cancer. Positive relationships between malaria and virus-associated cancers are relatively well-documented; for example, malaria can reactivate the Epstein-Barr Virus, which is the known cause of endemic Burkitt lymphoma. Nevertheless, possible anti-tumour properties of malaria have also been reported and, interestingly, this disease has long been thought to be beneficial to patients suffering from cancers. Current knowledge of the potential pro- and anti-cancer roles of malaria suggests that, contrary to other eukaryotic parasites affecting humans, Plasmodium-related cancers are principally lymphoproliferative disorders and attributable to virus reactivation, whereas, similar to other eukaryotic parasites, the anti-tumour effects of malaria are primarily associated with carcinomas and certain sarcomas. Moreover, malarial infection significantly suppresses murine cancer growth by inducing both innate and specific adaptive anti-tumour responses. This review aims to present an update regarding the ambivalent association between malaria and cancer, and further studies may open future pathways to develop novel strategies for anti-cancer therapies.

show abstract

Murine Plasmodium chabaudi Malaria Increases Mucosal Immune Activation and the Expression of Putative HIV Susceptibility Markers in the Gut and Genital Mucosae

Cited by 6 publications

References 40 publications

Evolutionarily Selected Overexpression of the Cytokine BAFF Enhances Mucosal Immune Response Against P. falciparum

Evolutionarily Selected Overexpression of the Cytokine BAFF Enhances Mucosal Immune Response Against P. falciparum

Inflammation and HIV Transmission in Sub-Saharan Africa

Puzzling and ambivalent roles of malarial infections in cancer development and progression

Contact Info

Product

Resources

About