Spontaneous Cytokine Production and Its Effect on Induced Production

Walker, Derrick; Jason, Janine; Wallace, Kelly; Slaughter, Justin; Whatley, Virginia; Han, Alison; Nwanyanwu, Okey; Kazembe, Peter N.; Dobbie, Hamish; Archibald, Lennox K.; Jarvis, William R.

doi:10.1128/cdli.9.5.1049-1056.2002

Cited by 26 publications

(35 citation statements)

References 24 publications

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“…The spontaneous production of cytokines by unstimulated PBMCs has been described previously in healthy persons living in developing countries where there is high prevalence of human immunodeficiency virus, as well as mycobacterial, malarial, and other parasitic infections (44)(45)(46)(47). Although IL-6 has been commonly associated with severe malaria (48)(49)(50), our study indicates the contrary, i.e., we found that significantly higher levels of this cytokine were present in animals that resisted severe malaria.…”

Section: Figcontrasting

confidence: 56%

Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

et al. 2016

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c Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n ‫؍‬ 8 each) and a schistosomiasis control group (n ‫؍‬ 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n ‫؍‬ 8) were intravenously inoculated with 10 5 Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P ‫؍‬ 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P ‫؍‬ 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria. P olyparasitism is common in low-resource countries, especially in sub-Saharan Africa. Coinfections may alter disease outcomes and affect both drug and vaccine efficacies (1, 2). The majority of studies on coinfections have focused on interactions between malaria and chronic helminth infections. Interest in studying malaria and schistosomiasis, in particular, comes from the major overlap of the two diseases in areas where they are endemic and the fact that these infections account for a large proportion of global morbidity and mortality (3, 4). Because of the chronicity of schistosome infection, most studies have focused on its impact on susceptibility to clinical malaria.Studies on malaria and schistosomiasis coinfections in human and animal models have generated contradicting results. Although some animal studies have shown that chronic schistosomiasis protects against severe malaria (5), others have reported that a concurrent schistosome infection enhances the severity of malaria (6-10). Many factors may account for these differences, including mouse strain, duration and intensity of the helminth infection, Plasmodium strain or species, inoculum size, or route of malaria infection (skin or blood stage) (11). An important limitat...

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Section: Figcontrasting

confidence: 56%

Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

et al. 2016

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“…2D). Spontaneous TNF production has been described in humans as well (40) and thus requires proper attention during the identification of recall T-cell responses responsible for vaccine-induced protection.…”

Section: Cd4mentioning

confidence: 99%

Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

Coppola

Eeden

Wilson

et al. 2015

Clin Vaccine Immunol

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Despite the availability of a vaccine and chemotherapeutic agents, tuberculosis (TB) remains the second leading cause of death from an infectious disease worldwide, annually causing around 9 million new cases and almost 2 million deaths (1). The highest burdens are found in low-income regions: Africa harbors about 25% of the world's TB cases and more than half have been counted in Asia (1). Furthermore, surveys with tuberculin skin tests (TST) suggest that one-third of the world's population is latently infected with Mycobacterium tuberculosis, which constitutes a huge reservoir with a 3 to 10% lifetime risk of developing TB (1, 2).It has long been recognized that the efficacy of vaccination with Mycobacterium bovis BCG, still the only registered TB vaccine, can be enhanced by a booster or replacement vaccine protecting against reactivating TB from latency (3). M. tuberculosis latency antigens (Ags), encoded by the DosR regulon, are upregulated in vitro under conditions that tubercle bacilli are thought to encounter in vivo during persistence in immunocompetent hosts (4) and in mouse models for latent M. tuberculosis infection (LTBI) (5). This discovery caused a change in focus in the search for a novel antigen(s) able to enhance long-term vaccine efficacy. Various human cohort studies showed preferential recognition of DosRencoded proteins, in particular Rv1733c, Rv2029c, Rv2627c, and Rv2628, by T cells from individuals with LTBI and to a lesser extent by TB patients (6-9). Also, latency antigens can induce CD4 ϩ and CD8 ϩ T cells in TST-converted individuals who were infected with M. tuberculosis decades ago in the preantibiotic era and yet never developed TB (10, 11).In mouse models using chronic, low-dose M. tuberculosis infection mimicking human LTBI, the preferential recognition of the DosR regulon in latent infection was further established (5) and provided evidence that BCG fails to induce a significant response to latency antigens despite their presence in the BCG genome. Also, a triple fusion protein, designated H56, including the latency/starvation antigen Rv2660 coupled to the early-stage proteins Ag85B and ESAT-6, provided protection by both pre-and postinfection vaccination in nonhuman primates (12,13). A similar improvement in long-term protection against M. tuberculosis was observed in mice after intradermal inoculation of recombinant BCG expressing the latency-associated antigens Rv2659c, Rv3407, and Rv1733c (14).Synthetic long peptides (SLPs), administered with adjuvants, are proven efficient vaccines for tumor therapy (15)(16)(17)(18)(19). Despite the success of this vaccine strategy, SLPs have not yet been applied to design new TB vaccines. Recognition of cognate antigen presented by either T cells or B cells will lead to an abortive proliferative response and death of the responding T cells.The immunogenicity of Rv1733c, which was the most commonly recognized latency antigen in M. tuberculosis-exposed household contacts from South Africa, Gambia, and Uganda (9), as well as the improved long...

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“…28 In addition, most cytokine-secreting cells also produce TNFa 13,[29][30][31][32][33] that makes it a good candidate as a universal marker to be used for the identification of cytokine-secreting cells. Up till now, the most commonly used cell surface marker to detect recently activated lymphocytes and other immune cells has been CD69.…”

Section: Discussionmentioning

confidence: 99%

A new simple whole blood flow cytometry-based method for simultaneous identification of activated cells and quantitative evaluation of cytokines released during activation

Rodríguez-Caballero

García‐Montero

Bueno

et al. 2004

Laboratory Investigation

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The multiple cellular and soluble elements of the immune system respond in a coordinated way, orchestrated by cytokines, to preserve the integrity of the organism. In this study, we describe a new and unique whole blood method that, with minimal sample manipulation, allows an overall evaluation of immune responses by simultaneously measuring cell activation and cytokine secretion. The identification of cells actively secreting cytokines is based on the stabilization of tumor necrosis factor a (TNFa) at the cell surface through the use of a specific inhibitor of the TNFa-converting enzyme. This inhibitor does not affect the release of cytokines other than TNFa and makes it possible to assess, in the same measurement, the phenotype of TNFa þ -secreting cells and quantify multiple secreted cytokines by using a specific and highly sensitive flow cytometry-based bead immunoassay. Upon stimulation of normal peripheral blood samples with either phorbol 12-myristate 13 acetate (PMA) plus ionomycin or lipopolysaccharide (LPS), both the number of TNFa þ cells and the amount of secreted cytokines progressively increased, the former becoming detectable first. After stimulation for 3 h with PMA plus ionomycin, cellular responses were associated with surface TNFa expression on the majority of CD3 þ T cells and secretion of Th1-associated cytokines: interferon c, interleukin (IL)-2, and to a lesser extent IL4. In turn, stimulation with LPS induced a response mainly by inflammatory cells. After 4 h of LPS-stimulation, the majority of CD14 þ monocytes showed surface TNFa expression; in parallel, high amounts of soluble IL1b, IL6, and IL8 became detectable. Likewise, stimulation of blood samples with cytomegalovirus (CMV) lysates induced viralspecific immune responses detectable in seropositive but not seronegative volunteers; such responses were associated with the detection of increased numbers of TNFa þ monocytes, TNFa þ /CD8 þ T cells and TNFa þ /CD8 À T lymphocytes in association with an increased secretion of IFNc, IL6 and TNFa.

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Spontaneous Cytokine Production and Its Effect on Induced Production

Cited by 26 publications

References 24 publications

Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

A new simple whole blood flow cytometry-based method for simultaneous identification of activated cells and quantitative evaluation of cytokines released during activation

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