Immunity to Paracoccidioides brasiliensis infection

Calich, Vera Lúcia Garcia; Vaz, Celidéia Aparecida Coppi; Burger, Eva

doi:10.1016/s0923-2494(98)80764-5

Cited by 93 publications

(89 citation statements)

References 35 publications

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“…Previous studies from our group have demonstrated the prevalence of Th2-regulated isotypes (IgG2b, IgG1, and IgA) in the most severe forms of the murine disease and a preferential production of the Th1-controlled isotype (IgG2a) in the benign infection (10,15,29). In this investigation, we verified that all isotypes of specific antibodies, except IgG2a, were produced in lower amounts by IL-4-deficient mice than by IL-4-sufficient C57BL/6 mice.…”

Section: Vol 72 2004 Pulmonary Pcm In Il-4-deficient Mice 2373mentioning

confidence: 82%

“…In vivo depletion of IL-4 did not alter the pattern of cytokines in the lungs but led to increased fungal load in the lungs of infected B10.A mice (10,16). In the C57BL/6 strain, however, equivalent treatment with anti-IL-4 monoclonal antibodies induced a less-severe pathology associated with increased production of pulmonary IFN-␥ (C. Arruda, R. C. Valente-Ferreira, A. Pina, and V. L. G. Calich, unpublished data).…”

Section: Vol 72 2004 Pulmonary Pcm In Il-4-deficient Mice 2373mentioning

confidence: 84%

“…This new cytokine balance would favor phagocyte activation and better control of fungal growth. Although a positive correlation between the presence of DTH reactions and protective immunity to murine and human PCM is usually found (10,20), in some experimental conditions this association is controversial and some researchers have claimed they are not causally related (27). Indeed, in pulmonary PCM of susceptible B10.A mice, depletion of CD8 ϩ T cells led to a more-severe disease concomitant with prominent DTH reactions, indicating a suppressive activity of CD8 ϩ T lymphocytes on the cellular immunity mediated by CD4 ϩ T cells (13).…”

Section: Vol 72 2004 Pulmonary Pcm In Il-4-deficient Mice 2373mentioning

confidence: 99%

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Absence of Interleukin-4 Determines Less Severe Pulmonary Paracoccidioidomycosis Associated with Impaired Th2 Response

et al. 2004

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Section: Vol 72 2004 Pulmonary Pcm In Il-4-deficient Mice 2373mentioning

confidence: 82%

Section: Vol 72 2004 Pulmonary Pcm In Il-4-deficient Mice 2373mentioning

confidence: 84%

Section: Vol 72 2004 Pulmonary Pcm In Il-4-deficient Mice 2373mentioning

confidence: 99%

See 1 more Smart Citation

Absence of Interleukin-4 Determines Less Severe Pulmonary Paracoccidioidomycosis Associated with Impaired Th2 Response

et al. 2004

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“…Anergy of delayed-type hypersensitivity reactions, elevated production of immunoglobulin G1 (IgG1) and IgG2b antibodies, impaired macrophage activation, and progressive infection were the main features of P. brasiliensis-infected B10.A mice. The immune response of resistant A/Sn mice was characterized by the preferential production of IgG2a antibodies, the presence of delayed-type hypersensitivity reactions, and efficient macrophage activation (10,11). When infected by the intratracheal (i.t.)…”

mentioning

confidence: 99%

Dual Role of Interleukin-4 (IL-4) in Pulmonary Paracoccidioidomycosis: Endogenous IL-4 Can Induce Protection or Exacerbation of Disease Depending on the Host Genetic Pattern

et al. 2004

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Resistance to paracoccidioidomycosis, the most important endemic mycosis in Latin America, is thought to be primarily mediated by cellular immunity and the production of gamma interferon. To assess the role of interleukin-4 (IL-4), a Th2 cytokine, pulmonary paracoccidioidomycosis in IL-4-depleted susceptible (B10.A) and intermediate (C57BL/6) mice was studied. Two different protocols were used to neutralize endogenous IL-4 in B10.A mice: 1 mg of anti-IL-4 monoclonal antibody (MAb)/week and 8 mg 1 day before intratracheal infection with 10 6 Paracoccidioides brasiliensis yeast cells. Unexpectedly, both protocols enhanced pulmonary infection but did not alter the levels of pulmonary cytokines and specific antibodies. Since in a previous work it was verified that C57BL/6 mice genetically deficient in IL-4 were more resistant to P. brasiliensis infection, we also investigated the effect of IL-4 depletion in this mouse strain. Treatment with the MAb at 1 mg/week led to less severe pulmonary disease associated with impaired synthesis of Th2 cytokines in the lungs and liver of control C57BL/6 mice. Conversely, in IL-4-depleted C57BL/6 mice, increased levels of tumor necrosis factor alpha and IL-12 were found in the lungs and liver, respectively. In addition, higher levels of immunoglobulin G2a (IgG2a) and lower levels of IgG1 antibodies were produced by IL-4-depleted mice than by control mice. Lung pathologic findings were equivalent in IL-4-depleted and untreated B10.A mice. In IL-4-depleted C57BL/6 mice, however, smaller and well-organized granulomas replaced the more extensive lesions that developed in untreated mice. These results clearly showed that IL-4 can have a protective or a diseasepromoting effect in pulmonary paracoccidioidomycosis depending on the genetic background of the host.

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“…The pattern of the immune response to P. brasiliensis is thought to be a determinant of disease progression and clinical outcome. Effective defense against P. brasiliensis depends mainly upon Th1 response, where TNF-a and IFN-g play a particularly prominent role (2).…”

mentioning

confidence: 99%

Phenotypic and Functional Characterization of NK Cells in Human Immune Response against the Dimorphic Fungus Paracoccidioides brasiliensis

Longhi

Silva

Fornazim

et al. 2012

The Journal of Immunology

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Besides their role in fighting viral infection and tumor resistance, recent studies have shown that NK cells also participate in the immune response against other infectious diseases. The aim of this study was to characterize the possible role of NK cells in the immune response against Paracoccidioides brasiliensis. Purified NK cells from paracoccidioidomycosis patients and healthy individuals were incubated with P. brasiliensis yeast cells or P. brasiliensis-infected monocytes, with or without the addition of recombinant IL-15. We found that NK cells from paracoccidioidomycosis patients exhibit a lower cytotoxic response compared with healthy individuals. NK cells are able directly to recognize and kill P. brasiliensis yeast cells, and this activity seems to be granule-dependent but perforin-independent, whereas the cytotoxicity against P. brasiliensis-infected monocytes is perforin-dependent. These results indicate that NK cells participate actively in the immune response against the P. brasiliensis infection either by directly destroying yeast cells or by recognizing and killing infected cells. Granulysin is the possible mediator of the cytotoxic effect, as the reduced cytotoxic activity against the yeast cells detected in patients with paracoccidioidomycosis is accompanied by a significantly lower frequency of CD56+granulysin+ cells compared with that in healthy controls. Furthermore, we show that NK cells released granulysin in cultures after being stimulated by P. brasiliensis, and this molecule is able to kill the yeast cells in a dose-dependent manner. Another important finding is that stimulated NK cells are able to produce proinflammatory cytokines (IFN-γ and TNF-α) supporting their immunomodulatory role in the infection.

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Immunity to Paracoccidioides brasiliensis infection

Cited by 93 publications

References 35 publications

Absence of Interleukin-4 Determines Less Severe Pulmonary Paracoccidioidomycosis Associated with Impaired Th2 Response

Absence of Interleukin-4 Determines Less Severe Pulmonary Paracoccidioidomycosis Associated with Impaired Th2 Response

Dual Role of Interleukin-4 (IL-4) in Pulmonary Paracoccidioidomycosis: Endogenous IL-4 Can Induce Protection or Exacerbation of Disease Depending on the Host Genetic Pattern

Phenotypic and Functional Characterization of NK Cells in Human Immune Response against the Dimorphic Fungus Paracoccidioides brasiliensis

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