Systems immunology of human malaria

Tran, Tuan M.; Samal, Babru; Kirkness, Ewen F.; Crompton, Peter D.

doi:10.1016/j.pt.2012.03.006

Cited by 36 publications

(29 citation statements)

References 106 publications

(145 reference statements)

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“…Thus, some peripheral blood cells (neutrophils, macrophages, natural killers, etc.) (6) and lymphocyte subsets are thought to play a major role in malarial parasite control (1,33).…”

Section: Discussionmentioning

confidence: 99%

CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

2015

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Tryptophan-rich proteins play important biological functions for the Plasmodium parasite. Plasmodium vivax contains remarkably large numbers of such proteins belonging to the "Pv-fam-a" family that need to be characterized. Earlier, we reported the presence of memory T cells and naturally acquired antibodies against 15 of these proteins in P. vivax malaria-exposed individuals (M. Zeeshan, H. Bora, and Y. D. Sharma, J Infect Dis 207:175-185, 2013, http://dx.doi.org/10.1093/infdis/jis650). Here, we sought to characterize and ascertain the cross talk between effector responses of T and B cells in malarial patients against all Pvfam-a family proteins. Therefore, we expressed the remaining 21 of these proteins in Escherichia coli and studied the humoral and cellular immune responses based on the same parameters used in our previous study. Naturally acquired IgG antibodies were detected against all 21 antigens in P. vivax patient sera (37.7 to 94.4% seropositivity). These antigens were able to activate the lymphocytes of P. vivax-exposed individuals, and the activated CD4 ؉ T lymphocytes produced higher levels of Th1 (interleukin-2 [IL-2] and gamma interferon [IFN-␥]) and Th2 (IL-4 and IL-10) cytokines than the healthy controls, but the response was Th2 biased. The combined results of present and previous studies seem to suggest a striking link between induction of the CD4 ؉ T cell response and naturally acquired antibodies against all 36 proteins of the Pv-fam-a family, the majority of them having conserved sequences in the parasite population. Further work is required to utilize this information to develop immunotherapeutic treatments for this disease. Despite continued efforts to control malaria, it remains a major health problem in affected tropical countries. There is an urgent need to develop an effective malaria vaccine and newer antimalarial drugs to control this disease. This requires the identification and characterization of newer parasite molecules that play significant biological function for the survival of the parasite and could generate cellular and humoral immune responses in humans to provide protection against the disease. Previous studies have shown that humoral and T-cell-mediated immune responses are induced against malaria parasite, and these responses were found to be antigen and stage specific (1). Antibodies come to play their role as soon as the parasite enters the human body. These antibodies not only clear the parasite by opsonization but also block the invasion of host cells by the parasite. Therefore, the humoral immune response plays a critical role in controlling the parasite.A role for dendritic cells, monocyte/macrophages, B cells, and several groups of T cells has been proposed in the cellular immune response against malaria (1-4). Some specific cytokines are produced from peripheral blood mononuclear cells in response to parasite infection, which further activates the host's macrophages, neutrophils, T cells, and natural killer cells to react against the parasites (5). Monocytes/ma...

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“…Thus, some peripheral blood cells (neutrophils, macrophages, natural killers, etc.) (6) and lymphocyte subsets are thought to play a major role in malarial parasite control (1,33).…”

Section: Discussionmentioning

confidence: 99%

CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

2015

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“…In contrast to what is typically available to researchers of other infectious diseases, the malaria research community has access to longitudinal ‘models’ of both experimental and natural P. falciparum infection in humans (23–25). Under strictly controlled conditions, volunteers are exposed to the bites of laboratory-reared P. falciparum -infected mosquitoes.…”

Section: Human Immunity and Malariamentioning

confidence: 99%

Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease

Crompton

Moebius

Portugal

et al. 2014

Annu. Rev. Immunol.

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269

248

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Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa family, the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world’s most vulnerable populations, claiming the lives of nearly a million children and pregnant women each year in Africa alone. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite’s complex life cycle with a view towards developing the tools that will contribute to the prevention of disease and death and ultimately the goal of malaria eradication. In so doing we hope to inspire immunologists to participate in defeating this devastating disease.

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“…Therefore, new strategies such as whole genome sequencing of Fulani vs. Dogon; systems immunology approaches to compare host immune response in unbiased manner through RNA-seq analysis and protein microarrays would be great of interest to elucidate the mechanisms of protection (Tran et al, 2012).…”

Section: Research Gaps On Sympatric Ethnicity Difference In Susceptibmentioning

confidence: 99%

Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?

et al. 2015

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Systems immunology of human malaria

Cited by 36 publications

References 106 publications

CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease

Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?

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Systems immunology of human malaria

Cited by 36 publications

References 106 publications

CD4 + T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

CD4 + T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease

Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?

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CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens