Neutrophil depletion during Toxoplasma gondii infection leads to impaired immunity and lethal systemic pathology.

نویسندگان

  • S K Bliss
  • L C Gavrilescu
  • A Alcaraz
  • E Y Denkers
چکیده

The immunomodulatory role of neutrophils during infection with Toxoplasma gondii was investigated. Monoclonal antibody-mediated depletion revealed that neutrophils are essential for survival during the first few days of infection. Moreover, neutrophil depletion was associated with a weaker type 1 immune response as measured by decreased levels of gamma interferon, interleukin-12 (IL-12) and tumor necrosis factor alpha. IL-10 was also decreased in depleted animals. Additionally, splenic populations of CD4(+) T cells, CD8(+) T cells, and NK1.1(+) cells were decreased in depleted mice. Neutrophil-depleted mice exhibited lesions of greater severity in tissues examined and a greater parasite burden as determined by histopathology and reverse transcription-PCR. We conclude that neutrophils are critical near the time of infection because they influence the character of the immune response and control tachyzoite replication.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Toxoplasma gondii triggers granulocyte-dependent cytokine-mediated lethal shock in D-galactosamine-sensitized mice.

To investigate the capacity of Toxoplasma gondii to induce cytokine-mediated toxicity, we employed a murine model of lethal shock in which hypersensitivity to microbial toxins is induced by D-galactosamine (D-Gal). Animals injected with D-Gal and tachyzoite lysate died within 12 to 24 h, whereas administration of D-Gal or lysate alone was nonlethal. Analyses of plasma cytokines revealed peaks o...

متن کامل

Inflammatory monocytes but not neutrophils are necessary to control infection with Toxoplasma gondii in mice.

Previous studies have suggested that both inflammatory monocytes and neutrophils are important for controlling acute toxoplasmosis in the mouse model. To test the role of these cell types, we used monoclonal antibody (MAb) RB6-8C5 to deplete both subsets of cells or MAb 1A8 to selectively remove neutrophils. RB6-8C5 MAb-treated mice succumbed to oral infection with Toxoplasma gondii, similar to...

متن کامل

A GRA1 DNA vaccine primes cytolytic CD8(+) T cells to control acute Toxoplasma gondii infection.

Protective immunity against Toxoplasma gondii is known to be mediated mainly by T lymphocytes and gamma interferon (IFN-gamma). The contribution of CD4(+) and CD8(+) T-lymphocyte subsets to protective immune responses against T. gondii infection, triggered by a GRA1 (p24) DNA vaccine, was assessed in this study. In vitro T-cell depletion experiments indicated that both CD4(+) and CD8(+) T-cell ...

متن کامل

Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th1 host immune responses in the absence of parasite replication.

A single inoculation of mice with the live, attenuated Toxoplasma gondii uracil auxotroph strain cps1-1 induces long-lasting immunity against lethal challenge with hypervirulent strain RH. The mechanism for this robust immunity in the absence of parasite replication has not been addressed. The mechanism of long-lasting immunity, the importance of route of immunization, cellular recruitment to t...

متن کامل

Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection.

We investigated the role of interleukin-17 (IL-17)/IL-17 receptor (IL-17R)-mediated signaling in the protective immunity against Toxoplasma gondii. IL-17R(-/-) mice developed a normal adaptive immunity against the parasite. However, increased mortality in the knockout animals can be attributed to a defect in the migration of polymorphonuclear leukocytes to infected sites during early infection.

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Infection and immunity

دوره 69 8  شماره 

صفحات  -

تاریخ انتشار 2001