Marco Campos - Academia.edu (original) (raw)

Papers by Marco Campos

Mediators of Inflammation, 2004

TRYPANOSOMA cruzi is the etiologic agent of Chagas' disease, a parasitic disease of enormous impo... more TRYPANOSOMA cruzi is the etiologic agent of Chagas' disease, a parasitic disease of enormous importance in Latin America. Herein we review the studies that revealed the receptors from innate immunity that are involved in the recognition of this protozoan parasite. We showed that the recognition of T. cruzi and its components occurs through Toll-like receptors (TLR) 2/CD14. Further, we showed in vivo the importance of the myeloid differentiation factor (MyD88), an adapter protein essential for the function of TLRs, in determining the parasitemia and mortality rate of mice infected with T. cruzi . We also discuss the implications of these findings in the pathophysiology of Chagas' disease.

TLRs function as pattern recognition receptors in mammals and play an essential role in the recog... more TLRs function as pattern recognition receptors in mammals and play an essential role in the recognition of microbial components. We found that the injection of glycoinositolphospholipids (GIPLs) from Trypanosoma cruzi into the peritoneal cavity of mice induced neutrophil recruitment in a TLR4-dependent manner: the injection of GIPL in the TLR4-deficient strain of mice (C57BL/ 10ScCr) caused no inflammatory response. In contrast, in TLR2 knockout mice, neutrophil chemoattraction did not differ significantly from that seen in wild-type controls. GIPL-induced neutrophil attraction and MIP-2 production were also severely affected in TLR4-mutant C3H/HeJ mice.

Immunological Reviews, 2004

Different studies have illustrated the activation of the innate immune system during infection wi... more Different studies have illustrated the activation of the innate immune system during infection with protozoan parasites. Experiments performed in vivo also support the notion that innate immunity has a crucial role in resistance as well as pathogenesis observed during protozoan infections such as malaria, leishmaniasis, toxoplasmosis, and trypanosomiasis. While major advances have been made in the assignment of bacterial molecules as Toll-like receptors (TLRs) agonists as well as defining the role of the Toll/interleukin-1 receptor (TIR) signaling pathway in host resistance to bacterial infection, this research area is now emerging in the field of protozoan parasites. In this review, we discuss the recent studies describing parasite molecules as TLR agonists and those studies indicating the essential role of the TIR-domain bearing molecule named myeloid differentiation factor 88 in host resistance to infection with protozoan parasites. Together, these studies support the hypothesis that the TIR signaling pathway is involved in the initial recognition of protozoan parasites by the immune system of the vertebrate host, early resistance to infection, development of acquired immunity, as well as pathology observed during acute infection with this class of pathogens.

American Journal of Pathology, 2005

Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family, is the major cau... more Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family, is the major cause of sporadic lethal encephalitis and blindness in humans. Recent studies have shown the importance of Toll-like receptors (TLRs) in the immune response to HSV-1 infection. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein that is downstream to mediated TLR activation and is essential for the production of inflammatory cytokines. Here, we studied the relationship between MyD88 and HSV-1 using a purified HSV-1 isolated from a natural oral recurrent human infection. We observed the activation of TLR-2 by HSV-1 in vitro using Chinese hamster ovary cells stably transfected with a reporter gene. Interestingly, we found that only peritoneal macrophages from MyD88−/− mice, but not macrophages from TRL2−/− or from wild-type mice, were unable to produce tumor necrosis factor-α in response to HSV-1 exposure. Additionally, although TLR2−/− mice showed no enhanced susceptibility to intranasal infection with HSV-1, MyD88−/− mice were highly susceptible to infection and displayed viral migration to the brain, severe neuropathological signs of encephalitis, and 100% mortality by day 10 after infection. Together, our results suggest that innate resistance to HSV-1 is mediated by MyD88 and may rely on activation of multiple TLRs.

Microbes and Infection, 2002

Activation of cells from the innate immune system has an important role in host resistance to ear... more Activation of cells from the innate immune system has an important role in host resistance to early infection with the intracellular protozoan parasite, Trypanosoma cruzi. Here we review the studies that have identified and structurally characterized the glycosylphosphatidylinositol (GPI) anchors, as parasite molecules responsible for the activation of cells from the macrophage lineage. We also cover the studies that have identified the receptor, signaling pathways as well as the array of genes expressed in macrophages that are activated by these glycoconjugates. We discuss the possible implications of such response on the host resistance to T. cruzi infection and the pathogenesis of Chagas disease.

Neuroscience Letters, 2008

Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The d... more Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The development of experimental models of HSV-1 encephalitis is relevant for the comprehension of the immune mechanisms involved in this infection. C57BL/6 mice were inoculated intracranially with 104 PFU of neurotropic HSV-1. All animals developed signs of encephalitis and died until day 6 post-infection (pi). Using intravital microscopy, we demonstrated increased leukocyte rolling and adhesion in the brain microvasculature of infected mice at days 1, 3 and 5 pi. The infection was followed by a significant increase in chemokine levels, including CCL2, CCL3, CCL5, CXCL1 and CXCL9. TNF-α also showed a significant increase at day 3 pi. Histological analyses demonstrated diffuse meningoencephalitis characterized mainly by mononuclear cell infiltrates. The present model of HSV-1 encephalitis exhibits high mortality in the very first days of infection. Accordingly, there were increased rolling and adhesion of leukocytes along the brain endothelium wall and a high expression of chemokines in the central nervous system. These results corroborate the role of chemokines in leukocyte recruitment following HSV-1 infection in the central nervous system.

Journal of Clinical Microbiology, 2007

We examined the clinical and epidemiological aspects of one case of zoonotic human infection duri... more We examined the clinical and epidemiological aspects of one case of zoonotic human infection during a bovine vaccinia virus outbreak and characterized the causative agent as a vaccinia virus (VACV) strain.

Infection and Immunity, 2004

Mice. TLR4 mutants (C3H/HeJ) were obtained from FIOCRUZ (Rio de Janeiro, Brazil), and the control... more Mice. TLR4 mutants (C3H/HeJ) were obtained from FIOCRUZ (Rio de Janeiro, Brazil), and the control mice, C3H/HePas, were purchased from the University of São Paulo (São Paulo, Brazil) and maintained at the Federal University of Minas Gerais (Belo Horizonte, Brazil). TLR2 knockout mice and wild-type littermates (C57BL/6 ϫ 129/Ola) were kindly provided by Shizuo Akira from Osaka University in Japan. BALB/c mice at 6 to 8 weeks of age were obtained and maintained at CPqRR/FIOCRUZ (Belo Horizonte, Brazil).

American Heart Journal, 2010

Herpes simplex virus 1 (HSV-1) is a neurotropic DNA virus that is responsible for several clinica... more Herpes simplex virus 1 (HSV-1) is a neurotropic DNA virus that is responsible for several clinical manifestations in humans, including encephalitis. HSV-1 triggers toll-like receptors (TLRs), which elicit cytokine production. Viral multiplication and cytokine expression in C57BL/6 wild-type (WT) mice infected with HSV-1 were evaluated. Virus was found in the trigeminal ganglia (TG), but not in the brains of animals without signs of encephalitis, between 2 and 6 days postinfection (d.p.i.). Cytokine expression in the TG peaked at 5 d.p.i. TLR9−/− and TLR2/9−/− mice were more susceptible to the virus, with 60% and 100% mortality, respectively, as opposed to 10% in the WT and TLR2−/− mice. Increased levels of both CXCL10/IP-10 and CCL2/MCP-1, as well as reduced levels of interferon-γ and interleukin 1-β transcripts, measured in both the TG and brains at 5 d.p.i., and the presence of virus in the brain were correlated with total mortality in TLR2/9−/− mice. Cytokine alterations in TLR2/9−/− mice coincided with histopathological changes in their brains, which did not occur in WT and TLR2−/− mice and occurred only slightly in TLR9−/− mouse brain. Increased cellularity, macrophages, CD8 T cells producing interferon-γ, and expression levels of TLR2 and TLR9 were detected in the TG of WT-infected mice. We hypothesize that HSV-1 infection is controlled by TLR-dependent immune responses in the TG, which prevent HSV-1 encephalitis.