Neutrophil Depletion duringToxoplasma gondiiInfection Leads to Impaired Immunity and Lethal Systemic Pathology

Abstract

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.The immune system is a complex nonlinear system, involving the coordination of multiple cell types. Disease often results from an insufficient immune response. Lack of protection can occur when any one or more of the components of the immune system are impaired. Neutropenia is a risk factor associated with Aspergillus fumigatus, Candida albicans, Strongyloides ratti, Yersinia enterocolitica, Chlamydia trachomatis, Mycobacterium tuberculosis, Listeria monocytogenes, and Toxoplasma gondii infections (2,3,5,7,8,22,27,31,41). In some cases, neutropenia has been correlated with impaired protective acquired immunity, suggesting that neutrophils function as immunomodulators of acquired immunity (27, 31). The list of microbes affected by the actions of neutrophils is ever-growing, and it is evident that these cells are involved in the immune response to a highly diverse array of both intracellular and extracellular pathogens.We examined the development of immunity during T. gondii infection in mice depleted of neutrophils by monoclonal antibody (MAb) administration. T. gondii is an obligate intracellular protozoan parasite that poses an important public health risk. Congenital infections may result in severe birth defects, and reactivation of chronic infection can lead to development of encephalitis, a particular problem for persons who are immunosuppressed (25, 28). We found that neutrophil depletion at the time of infection led to development of lesions in multiple organs, including the spleen, lung, liver, and brain, and was associated with an impaired ability to produce early gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣) and interleukin-12 (IL-12). Splenic populations of T cells and NK cells were decreased in neutrophil-depleted infected mice. Moreover, neutrophil-depleted mice harbored an increased parasite burden. We conclude that neutrophils are important immunomodulators early in the course of T. gondii infection and play a critical role in protecting the host from uncontrolled tachyzoite replication. MATERIALS AND METHODSMice. C57BL/6 female mice (6 to 12 weeks of age) were obtained fro...

TNF‐α mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis

“…These data corroborate evidence showing that the induction of iNOS in different cell types or different tissues is controlled by a different pattern of cytokines [18]. Despite demonstrations that L. major is able to infect neutrophils ([14] and present results) and that these cells are involved in the control of infection caused by L. major [14], L. amazonensis [19] and L. infantum [13], as well as by other parasites such T. gondii [20], the mechanism involved in the neutrophil-mediated killing of L. major has not been shown. The fact that neutrophils kill microorganisms such as Candida albicans by a mechanism dependent on NO production [21] and the presence of neutrophils expressing iNOS in the lesion of L. major-infected mice suggest that these cells might be involved in the control of parasite growth in the anti-TNF- § -treated mice by a mechanism dependent on NO production.…”

Motile invaded neutrophils in the small intestine ofToxoplasma gondii-infected mice reveal a potential mechanism for parasite spread

“…Neutrophils produce IL-12 and generate neutrophil extracellular traps in response to T. gondii infection, suggesting a host-protective role (49)(50)(51). Antibodymediated neutrophil depletion and genetic disruption of neutrophil recruitment support this notion (52)(53)(54). However, it was demonstrated recently that the depleting antibody used in some of these studies also eliminated IMs, which are critical for control of parasite growth (47).…”

Análise morfométrica da parede intestinal e dinâmica de mucinas secretadas no íleo de frangos infectados por Toxoplasma gondii

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