Determination of intracellular cytokines produced by Th1 and Th2 cells using flow cytometry in patients with brucellosis

Akbulut, Handan; Kılıç, Süleyman; Bulut, Vedat; Özden, Mehmet

doi:10.1016/j.femsim.2005.04.001

Cited by 20 publications

(22 citation statements)

References 24 publications

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“…17,18 It has been reported that pretreatment CD3 + IFN-γ + levels were higher in responsive patients than the unresponsive group. 19 In addition to the studies showing induction of Th1-type immune response by brucellosis; Galanakis et al, 4 have reported that in children with brucellosis, serum IL-4 levels increased in the acute phase of the disease. In our study, IL-1 β and IL-4 levels were not statistically different between patient and control groups.…”

Section: Discussionmentioning

confidence: 98%

Cytokine levels in patients with <i>Brucellosis</i> and their relations with the treatment

Akbulut¹,

Çelik²,

Akbulut³

2007

Indian J Med Microbiol

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Section: Discussionmentioning

confidence: 98%

Cytokine levels in patients with <i>Brucellosis</i> and their relations with the treatment

Akbulut¹,

Çelik²,

Akbulut³

2007

Indian J Med Microbiol

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“…The response of the immune system to Brucella is complex and involves innate and adaptive immunity (2). The focus of our work was to investigate the pattern of circulating cytokines in brucellosis patients.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the pattern of T-lymphocyte cytokine secretion is considered to be critical for the effectiveness of the protective anti-Brucella immune response (3, 7). It has been postulated that Th1 cytokines confer resistance, while Th2 cytokines facilitate the development of brucellosis (2,3,24,25,40,43,52). In animal models, gamma interferon (IFN-␥) induces macrophage activation and control of Brucella infection (16,18,43).…”

mentioning

confidence: 99%

Human Brucellosis Is Characterized by an Intense Th1 Profile Associated with a Defective Monocyte Function

et al. 2010

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In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex-and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1␤ (IL-1␤), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzymelinked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-␥, IL-2, and TNF-␣, but not that of IL-4, by phorbol myristate-activated CD4 ؉ CD3 ؉ and CD8 ؉ CD3 ؉ T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-␥ levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes.Brucellosis is a zoonotic disease of worldwide distribution. Despite its control in many countries, it remains endemic in the Mediterranean and Middle Eastern regions (20,28,41,42). Brucella melitensis is the most frequent cause of human brucellosis in these geographical areas (19). In Spain, it has been reported that the majority (more than 97.5%) of isolates were identified as Brucella melitensis (13,44,45).Brucella organisms are facultatively intracellular Gram-negative coccobacilli that reside and replicate in a vacuolar compartment within myelomonocytic cells of the infected host (14,15,47). The response to Brucella involves the whole gamut of the immune system, from innate to adaptive immunity (21). In murine models, passive transfer of immune cells resulted in an effective antiBrucella defensive response mediated by CD4 ϩ and CD8 ϩ T lymphocytes (5, 6, 32, 37, 51, 52). Furthermore, the pattern of T-lymphocyte cytokine secretion is considered to be critical for the effectiveness of the protective anti-Brucella immune response (3, 7). It has been postulated that Th1 cytokines confer resistance, while Th2 cytokines facilitate the development of brucellosis (2,3,24,25,40,43,52). In animal models, gamma interferon (IFN-␥) induces macrophage activation and control of Brucella infection (16,18,43). In Brucella-infected mice, administration of recombinant IFN-␥ enhances host resistance, resulting in a deep decrease in the number of viable bacteria (51). Moreover, host IFN-␥ de...

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“…Clonal T cell expansion is initiated with production of interleukin-2 (IL-2) and interleukin-12 (IL-12), which initiates a CD8+ cytotoxic response on Brucella -infected cells. Infected macrophages produce IL-12 and IFN-γ which regulate antigen presentation and may contribute to the limitation of intracellular bacterial replication through unknown mechanisms (Akbulut et al, 2005). Data also suggest that Brucella spp.…”

Section: T Cell Cytokine Responses To Brucella Infectionmentioning

confidence: 99%

Antigen-Specific Acquired Immunity in Human Brucellosis: Implications for Diagnosis, Prognosis, and Vaccine Development

Cannella¹,

Tsolis²,

Liang³

et al. 2012

Front. Cell. Inf. Microbio.

106

134

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Brucella spp., are Gram negative bacteria that cause disease by growing within monocyte/macrophage lineage cells. Clinical manifestations of brucellosis are immune mediated, not due to bacterial virulence factors. Acquired immunity to brucellosis has been studied through observations of naturally infected hosts (cattle, goats), mouse models (mice), and human infection. Even though Brucella spp. are known for producing mechanisms that evade the immune system, cell-mediated immune responses drive the clinical manifestations of human disease after exposure to Brucella species, as high antibody responses are not associated with protective immunity. The precise mechanisms by which cell-mediated immune responses confer protection or lead to disease manifestations remain undefined. Descriptive studies of immune responses in human brucellosis show that TH1 (interferon-γ-producing T cells) are associated with dominant immune responses, findings consistent with animal studies. Whether these T cell responses are protective, or determine the different clinical responses associated with brucellosis is unknown, especially with regard to undulant fever manifestations, relapsing disease, or are associated with responses to distinct sets of Brucella spp. antigens are unknown. Few data regarding T cell responses in terms of specific recognition of Brucella spp. protein antigens and peptidic epitopes, either by CD4+ or CD8+ T cells, have been identified in human brucellosis patients. Additionally because current attenuated Brucella vaccines used in animals cause human disease, there is a true need for a recombinant protein subunit vaccine for human brucellosis, as well as for improved diagnostics in terms of prognosis and identification of unusual forms of brucellosis. This review will focus on current understandings of antigen-specific immune responses induced Brucella peptidic epitopes that has promise for yielding new insights into vaccine and diagnostics development, and for understanding pathogenetic mechanisms of human brucellosis.

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Determination of intracellular cytokines produced by Th1 and Th2 cells using flow cytometry in patients with brucellosis

Cited by 20 publications

References 24 publications

Cytokine levels in patients with <i>Brucellosis</i> and their relations with the treatment

Cytokine levels in patients with <i>Brucellosis</i> and their relations with the treatment

Human Brucellosis Is Characterized by an Intense Th1 Profile Associated with a Defective Monocyte Function

Antigen-Specific Acquired Immunity in Human Brucellosis: Implications for Diagnosis, Prognosis, and Vaccine Development

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