Human immune responses to Plasmodium falciparum infection: molecular evidence for a suboptimal THαβ and TH17 bias over ideal and effective traditional TH1 immune response

Hu, Wan-Chung

doi:10.1186/1475-2875-12-392

Cited by 32 publications

(32 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and Thαβ bias over Th1, with these Th17 and Thαβ responses being ineffective against the parasite [5]. These differences may be explained by the different study methods, with the former study looking at gene expressions [5] immune response may not be predominant in P. falciparum as the parasite was not cleared as expected for predominant Th1 immune response.…”

Section: Discussionmentioning

confidence: 99%

“…These differences may be explained by the different study methods, with the former study looking at gene expressions [5] immune response may not be predominant in P. falciparum as the parasite was not cleared as expected for predominant Th1 immune response. This has been evident in the current study, where the independent P. falciparum had higher parasitaemia than in the co-infection (F(8, 12) = 3.841, p = 0.0362) ( Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…The sample size calculation indicated that a minimum sample size of 40 was required as [5] with significance level at α = 0.05 and power of 80%. After screening the 120 eligible participants, 40 individuals were enrolled to perform T helper phenotyping from their PBMCs.…”

Section: Study Design and Participantsmentioning

confidence: 99%

“…They are parasitic infections causing leading public health problems in sub-Saharan Africa, mostly affecting children [1] [2] [3]. P. falciparum and S. mansoni infections initiate a T helper immune response [4] [5], which links the innate and adaptive immune responses against the parasites. The T helper human immune response to infections can be categorized into Th1, Th2 and Th17.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Schistosoma mansoni Infection: A Major Contributor of Reduced Effective T Helper Responses against Plasmodium falciparum and Schistosoma mansoni Co-Infection in ex vivo: A Cross-Sectional Study to Assess Th1, Th2 & Th17 Immune Responses

Rowel¹,

Nabatanzi²,

Olobo³

et al. 2017

OJI

View full text Add to dashboard Cite

Background: Parasitic worms evade immune responses, and interactions between diseases can cause altered immunologic outcomes compared to what usually occurs with single infections. These interactions may influence vaccine and chemotherapeutic efficacy. Schistosoma mansoni and Plasmodium falciparum are co-endemic in Uganda and are the leading parasitic causes of public health problems across sub-Saharan Africa. Objectives: The overall aim was therefore, to elucidate the impact of S. mansoni infection on protective T helper immune responses on P. falciparum and S. mansoni co-infection. Methodology: This study evaluated the T helper immune responses in individuals with independent S. mansoni infection, independent P. falciparum infection, co-infection and non-infection in school attending children in a co-endemic area along Lake Victoria shores, Uganda. Immune responses were categorized into Th1, Th2, and Th17 based on unique cytokine(s) produced by the T helper subpopulation in ex vivo. Kato Katz thick smears and circulating cathodic antigen tests were performed for S. mansoni screening, whereas thick and thin blood smear techniques were performed for P. falciparum screening.Results: We observed an up regulated Th1 T helper subpopulation in independent P. falciparum infections compared to the uninfected group. Suboptimal T helper immune responses were detected in independent S. mansoni How to cite this paper: Rowel, C., Nabatanzi, R., Olobo, J., Auma, A., Asiimwe, B., Mbabazi, O., Bayiyana, A., Enzaru, A. and 19infections characterized by significantly down regulated Th1 (Z = −1.425, p = 0.0313) response in comparison to the non-infected group. Suboptimal T helper immune responses were also recorded in the co-infected individuals characterized by significantly down regulated Th1 (Z = −3.260, p = 0.0273) and Th2 (Z = −1.180, p = 0.0078) responses compared to independent P. falciparum. Conclusions: S. mansoni infection is a major contributor of a reduced effective T helper immune response against P. falciparum in P. falciparum and S. mansoni co-infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Study Design and Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Schistosoma mansoni Infection: A Major Contributor of Reduced Effective T Helper Responses against Plasmodium falciparum and Schistosoma mansoni Co-Infection in ex vivo: A Cross-Sectional Study to Assess Th1, Th2 & Th17 Immune Responses

Rowel¹,

Nabatanzi²,

Olobo³

et al. 2017

OJI

View full text Add to dashboard Cite

show abstract

“…Plasmodium falciparum causes the most severe form of malaria with complications that include cerebral malaria, pulmonary edema, acute renal failure, or severe anemia (Buffet et al., ; Das, ; Medana & Turner, ; Mohan, Sharma, & Bollineni, ) . P. falciparum malaria is frequently associated with immunosuppression and increased secondary infections (Hu, ; Ihekwereme, Esimone, & Nwanegbo, ; Orf & Cunnington, ; Troye‐Blomberg & Perlmann, ). Immunosuppression enhances parasitemia and reduces immune responses to not only malaria parasite proteins but other pathogens as well.…”

Section: Introductionmentioning

confidence: 99%

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

et al. 2018

View full text Add to dashboard Cite

Plasmodium falciparum malaria is the most severe form of malaria with several complications. The malaria pigment-hemozoin (Hz) is associated with severe anemia, cytokine dysfunction, and immunosuppression, thus making it an interesting target for developing new strategies for antimalarial therapy. Monocytes (MO) in circulation actively ingest Hz released by Plasmodium parasites and secrete pro- and anti-inflammatory cytokines. M1 and M2 types represent the two major forms of MO/macrophages (MQ) with distinct phenotypes and opposing functions. Imbalance in the polarization of these types is reported in many infectious diseases. Though the association of Hz with immunosuppression is well documented, its role in activation of MO in context of M1/M2 phenotypes remains to be addressed. We report here that natural Hz drives human MO toward M2-like phenotype as evidenced by the expression of M2 signature markers. Hz-fed MO showed elevated transcript and secreted level of IL-10, CCL17, CCL1, expression of mannose-binding lectin receptor (CD206), and arginase activity. Hz attenuated HLA-DR expression, nitric oxide, and reactive oxygen species production, which are the features of M1 phenotype. Our data also implicate the involvement of p38 MAPK, PI3K/AKT, and NF-κB signaling pathways in skewing of Hz-fed MO toward M2-like type and suppression of mitogen-stimulated lymphocyte proliferation. Importantly, antimalarial drugs-chloroquine and artemisinin-partially reversed activation of Hz-induced MO toward M2-like phenotype. Considering the limitations in the current therapeutic options for malaria, we propose that these drugs may be re-examined for their potential as immunomodulators and candidates for adjunctive treatment in malaria.

show abstract

Blessing or curse? Proteomics in granzyme research

Joeckel

Bird

2014

Proteomics Clinical Apps

View full text Add to dashboard Cite

Granzymes (gzms) are a group of serine proteases that play an important role in innate and adaptive immunity, blood coagulation, apoptosis, and inflammation, but are also connected to atherosclerosis, diabetes, cardiovascular and inflammatory lung diseases, cancer, and sepsis. Humans have five gzms (gzms A, B, H, K, and M), which differ in their substrate specificity. It is widely accepted that they are delivered from cytotoxic lymphocytes via perforin into the cytoplasm of target cells where they initiate cell death, modulate cytokine signaling, or inactivate pathogen proteins. However, more recent evidence indicates gzms also act extracellularly in noncytotoxic processes. Proteomic approaches are directed at mapping gzm cleavage specificity, identifying substrates, and unraveling the (patho-) physiological role of these proteases. These studies have refined our understanding of gzm species specificity, and collectively uncovered an enormous number of new substrates. However, with the exception of a very few human gzmB substrates supported by independent data (Bid, DNA-PK, PARP, ICAD, and procaspase 7), it is presently unclear which are physiologically relevant. This review aims to summarize and analyze the different proteomic approaches used and discuss both their convincing and controversial outcomes.

show abstract

Human immune responses to Plasmodium falciparum infection: molecular evidence for a suboptimal THαβ and TH17 bias over ideal and effective traditional TH1 immune response

Cited by 32 publications

References 38 publications

<i>Schistosoma mansoni</i> Infection: A Major Contributor of Reduced Effective T Helper Responses against <i>Plasmodium falciparum</i> and <i>Schistosoma mansoni</i> Co-Infection in <i>ex vivo</i>: A Cross-Sectional Study to Assess Th1, Th2 & Th17 Immune Responses

<i>Schistosoma mansoni</i> Infection: A Major Contributor of Reduced Effective T Helper Responses against <i>Plasmodium falciparum</i> and <i>Schistosoma mansoni</i> Co-Infection in <i>ex vivo</i>: A Cross-Sectional Study to Assess Th1, Th2 & Th17 Immune Responses

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

Blessing or curse? Proteomics in granzyme research

Contact Info

Product

Resources

About