The impaired pregnancy outcome in murine congenital toxoplasmosis is associated with a pro-inflammatory immune response, but not correlated with decidual inducible nitric oxide synthase expression

Coutinho, Loyane Bertagnolli; Gomes, A. da S.; Araújo, Ester Cristina Borges; Barenco, Paulo Victor Czarnewski; Santos, Jane Lima dos; Caixeta, Diego R.; Silva, Deise A. O.; Cunha-Júnior, Jair P.; Ferro, Eloísa Amália Vieira; Silva, Neide M.

doi:10.1016/j.ijpara.2012.01.006

Cited by 24 publications

(37 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During pregnancy, induction of a type-2 immune response has no effect on the pregnancy; however, induction of a type-1 response by parasitic infection can lead to abortion via alteration of the cytokine profile in the fetal-maternal interface [42]. In murine models of congenital toxoplasmosis, an imbalance in cytokine production and increased inflammatory responses are associated with increased apoptosis and necrosis at the site of implantation, leading to embryonic loss [43]. …”

Section: Discussionmentioning

confidence: 99%

Azithromycin is able to control Toxoplasma gondii infection in human villous explants

et al. 2014

View full text Add to dashboard Cite

BackgroundAlthough Toxoplasma gondii infection is normally asymptomatic, severe cases of toxoplasmosis may occur in immunosuppressed patients or congenitally infected newborns. When a fetal infection is established, the recommended treatment is a combination of pyrimethamine, sulfadiazine and folinic acid (PSA). The aim of the present study was to evaluate the efficacy of azithromycin to control T. gondii infection in human villous explants.MethodsCultures of third trimester human villous explants were infected with T. gondii and simultaneously treated with either PSA or azithromycin. Proliferation of T. gondii, as well as production of cytokines and hormones by chorionic villous explants, was analyzed.ResultsTreatment with either azithromycin or PSA was able to control T. gondii infection in villous explants. After azithromycin or PSA treatment, TNF-α, IL-17A or TGF-β1 levels secreted by infected villous explants did not present significant differences. However, PSA-treated villous explants had decreased levels of IL-10 and increased IL-12 levels, while treatment with azithromycin increased production of IL-6. Additionally, T. gondii-infected villous explants increased secretion of estradiol, progesterone and HCG + β, while treatments with azithromycin or PSA reduced secretion of these hormones concurrently with decrease of parasite load.ConclusionsIn conclusion, these results suggest that azithromycin may be defined as an effective alternative drug to control T. gondii infection at the fetal-maternal interface.

show abstract

Section: Discussionmentioning

confidence: 99%

Azithromycin is able to control Toxoplasma gondii infection in human villous explants

et al. 2014

View full text Add to dashboard Cite

show abstract

“…gondii by the oral route as previously described [43-45] and were treated for an additional 11 days with ZnPPIX or hemin or vehicle. The animals were observed daily for morbidity and body weight changes.…”

Section: Methodsmentioning

confidence: 99%

Heme oxygenase-1 activity is involved in the control of Toxoplasma gondii infection in the lung of BALB/c and C57BL/6 and in the small intestine of C57BL/6 mice

Araujo

Barbosa

Coutinho

et al. 2013

Vet Res

View full text Add to dashboard Cite

Heme oxygenase-1 (HO-1) is an enzyme that catabolizes free heme, which induces an intense inflammatory response. The expression of HO-1 is induced by different stimuli, triggering an anti-inflammatory response during biological stress. It was previously verified that HO-1 is able to induce indoleamine 2,3-dioxygenase (IDO), an enzyme that is induced by IFN-γ in Toxoplasma gondii infection. To verify the role of HO-1 during in vivo T. gondii infection, BALB/c and C57BL/6 mice were infected with the ME49 strain and treated with zinc protoporphyrin IX (ZnPPIX) or hemin, which inhibit or induce HO-1 activity, respectively. The results show that T. gondii infection induced high levels of HO-1 expression in the lung of BALB/c and C57BL6 mice. The animals treated with ZnPPIX presented higher parasitism in the lungs of both lineages of mice, whereas hemin treatment decreased the parasite replication in this organ and in the small intestine of infected C57BL/6 mice. Furthermore, C57BL/6 mice infected with T. gondii and treated with hemin showed higher levels of IDO expression in the lungs and small intestine than uninfected mice. In conclusion, our data suggest that HO-1 activity is involved in the control of T. gondii in the lungs of both mouse lineages, whereas the hemin, a HO-1 inducer, seems to be involved in the control of parasitism in the small intestine of C57BL/6 mice.

show abstract

“…Furthermore, T. gondii profilin interacts with TLR11 in mice, and cyclophilin binds the CCR5 receptor (Aliberti et al, 2003;Menzies et al, 2008). Thus, the recognition of T. gondii danger signals stimulates a cascade of innate cellular and soluble responses; robust NK cell activation, dendritic cell maturation, macrophage activation and production of IFN␥, IL-12, TNF␣ and iNOS which together limit parasite tachyzoite replication (Coutinho et al, 2012;Miller et al, 2009). Indeed dendritic cell activation following T. gondii infection in mice is rapid; within a few hours most splenic CD11c + cells have migrated from the red pulp to the T cell areas producing IL-12 (Miller et al, 2009).…”

Section: Toxoplasmosismentioning

confidence: 99%

“…2). Both these aspects have been examined in various strains of mice (Coutinho et al, 2012). C57BL/6 mice experience higher rates of resorptions than the BALB/c strain following T. gondii infection and this correlates to higher levels of decidual necrosis and systemic TNF-␣ levels (Coutinho et al, 2012).…”

Section: Toxoplasmosismentioning

confidence: 99%

From mice to women: the conundrum of immunity to infection during pregnancy

Krishnan

Nguyen

McComb

2013

Journal of Reproductive Immunology

View full text Add to dashboard Cite

Resistance to infection is the ability of the host to evoke a strong immune response sufficient to eliminate the infectious agent. In contrast, maternal tolerance to the fetus necessitates careful regulation of immune responses. Successful pregnancy requires the maternal host to effectively balance the opposing processes of maternal immune reactivity and tolerance to the fetus. However, this balance can be perturbed by infections which are recognized as the major cause of adverse pregnancy outcome including pre-term labor. Select pathogens also pose a serious threat of severe maternal illness. These include intracellular and chronic pathogens that have evolved immune evasive strategies. Murine models of intracellular bacteria and parasites that mimic pathogenesis of infection in humans have been developed. While human epidemiological studies provide insight into maternal immunity to infection, experimental infection in pregnant mice is a vital tool to unravel the complex molecular mechanisms of placental infection, congenital transmission and maternal illness. We will provide a comprehensive review of the pathogenesis of several infection models in pregnant mice and their clinical relevance. These models have revealed the immunological function of the placenta in responding to, and resisting infection. Murine feto-placental infection provides an effective way to evaluate new intervention strategies for managing infections during pregnancy, adverse fetal outcome and long-term effects on the offspring and mother.

show abstract

The impaired pregnancy outcome in murine congenital toxoplasmosis is associated with a pro-inflammatory immune response, but not correlated with decidual inducible nitric oxide synthase expression

Cited by 24 publications

References 45 publications

Azithromycin is able to control Toxoplasma gondii infection in human villous explants

Azithromycin is able to control Toxoplasma gondii infection in human villous explants

Heme oxygenase-1 activity is involved in the control of Toxoplasma gondii infection in the lung of BALB/c and C57BL/6 and in the small intestine of C57BL/6 mice

From mice to women: the conundrum of immunity to infection during pregnancy

Contact Info

Product

Resources

About