Seropositividad a Chlamydophila psittaci en cotorras argentinas (Myiopsitta monachus) invasoras de la ciudad de Santiago de Chile / Seropositivity to zoonotic Chlamydophila psittaci in invasive monk parakeets (Myiopsitta monachus) from Santiago, Chile

INTRODUCCIÓN: Chlamydophila psittaci es una bacteria zoonótica e intracelular estricta, que provoca la psitacosis humana y su principal hospedero son las aves psitácidas. La cotorra argentina es un ave psitácida nativa de Sudamérica y actualmente considerada una especie invasora en 19 países, incluyendo Chile. OBJETIVO: Determinar positividad contra C. psittaci en muestras de suero y torulados de cotorras argentinas de vida libre capturadas en la Región Metropolitana de Chile. MÉTODOS: Se analizaron 95 muestras de suero de pichones e individuos adultos de cotorras argentinas, a través de una prueba de ELISA indirecto utilizando un kit comercial. Posteriormente, se analizaron 40 tórulas nasotraqueales y cloacales de individuos adultos a través de una RPC en tiempo real específica para C. psittaci. RESULTADOS: Se detectaron anticuerpos en muestras de suero de cinco individuos adultos de cotorras argentinas (n = 68), mientras que ninguno de los pichones analizados fue seropositivo (n = 27). Todas las muestras analizadas a través de RPC en tiempo real fueron negativas. CONCLUSIÓN: Estos resultados demuestran por primera vez en Chile la exposición a C. psittaci en cotorras argentinas de vida libre, lo cual puede representar un riesgo importante para la transmisión de este patógeno a poblaciones humanas y animales.

BACKGROUND: Chlamydophila psittaci is a zoonotic obligate intracellular bacterium that causes the human psittacosis, and its main host are psittacine birds. The monk parakeet is a psittacine bird native to South America, currently being considered an invasive species in 19 countries, including Chile. AIM: To determine positivity to C. psittaci in serum samples and swabs from free-ranging monk parakeets captured in the Metropolitan Region of Chile. METHODS: Ninety-five serum samples from nestling chicks and adult monk parakeets were tested using an indirect ELISA test kit. Cloacal and nasotracheal swabs from 40 adult parakeets were further analyzed by C. psittaci-specific real-time PCR. RESULTS: We found antibody titers in sera of five adult monk parakeets (n = 68) while none of the nestlings were seropositive (n = 27). All samples tested with real-time PCR were negative. CONCLUSIONS: Our results demónstrate for the first time in Chile the exposure to C. psittaci in free-ranging monk parakeets which may represent a significant risk of pathogen transmission to human and animal populations.

The Interactions of Parasite Calreticulin With Initial Complement Components: Consequences in Immunity and Virulence.

Because of its capacity to increase a physiologic inflammatory response, to stimulate phagocytosis, to promote cell lysis and to enhance pathogen immunogenicity, the complement system is a crucial component of both the innate and adaptive immune responses. However, many infectious agents resist the activation of this system by expressing or secreting proteins with a role as complement regulatory, mainly inhibitory, proteins. Trypanosoma cruzi, the causal agent of Chagas disease, a reemerging microbial ailment, possesses several virulence factors with capacity to inhibit complement at different stages of activation. T. cruzi calreticulin (TcCalr) is a highly-conserved, endoplasmic reticulum-resident chaperone that the parasite translocates to the extracellular environment, where it exerts a variety of functions. Among these functions, TcCalr binds C1, MBL and ficolins, thus inhibiting the classical and lectin pathways of complement at their earliest stages of activation. Moreover, the TcCalr/C1 interaction also mediates infectivity by mimicking a strategy used by apoptotic cells for their removal. More recently, it has been determined that these Calr strategies are also used by a variety of other parasites. In addition, as reviewed elsewhere, TcCalr inhibits angiogenesis, promotes wound healing and reduces tumor growth. Complement C1 is also involved in some of these properties. Knowledge on the role of virulence factors, such as TcCalr, and their interactions with complement components in host-parasite interactions, may lead toward the description of new anti-parasite therapies and prophylaxis.

Trypanosoma cruzi Calreticulin: Immune Evasion, Infectivity, and Tumorigenesis.

To successfully infect, Trypanosoma cruzi evades and modulates the host immune response. T. cruzi calreticulin (TcCalr) is a multifunctional, endoplasmic reticulum (ER)-resident chaperone that, translocated to the external microenvironment, mediates crucial host-parasite interactions. TcCalr binds and inactivates C1 and mannose-binding lectin (MBL)/ficolins, important pattern- recognition receptors (PRRs) of the complement system. Using an apoptotic mimicry strategy, the C1-TcCalr association facilitates the infection of target cells. T. cruzi infection also seems to confer protection against tumorigenesis. Thus, recombinant TcCalr has important antiangiogenic properties, detected in vitro, ex vivo, and in ovum, most likely contributing at least in part, to its antitumor properties. Consequently, TcCalr is useful for investigating key issues of host-parasite interactions and possible new immunological/pharmacological interventions in the areas of Chagas' disease and experimental cancer.

Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin.

American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote) and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68), T. cruzi complement regulatory protein (TcCRP), trypomastigote decay-accelerating factor (T-DAF), C2 receptor inhibitor trispanning (CRIT) and T. cruzi calreticulin (TcCRT). Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH) and plasma membrane-derived vesicles (PMVs). All these proteins inhibit different steps of the classical (CP), alternative (AP) or lectin pathways (LP). Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host-parasite interplay. Thus, we have proposed that TcCRT is a pleiotropic molecule, present not only in the parasite endoplasmic reticulum, but also on the trypomastigote surface, participating in key processes to establish T. cruzi infection, such as inhibition of the complement system and serving as an important virulence factor. Additionally, TcCRT interaction with key complement components, participates as an anti-angiogenic and anti-tumor molecule, inhibiting at least in important part, tumor growth in infected animals.

Is the Antitumor Property of Trypanosoma cruzi Infection Mediated by Its Calreticulin?

Eight to 10 million people in 21 endemic countries are infected with Trypanosoma cruzi. However, only 30% of those infected develop symptoms of Chagas' disease, a chronic, neglected tropical disease worldwide. Similar to other pathogens, T. cruzi has evolved to resist the host immune response. Studies, performed 80 years ago in the Soviet Union, proposed that T. cruzi infects tumor cells with similar capacity to that displayed for target tissues such as cardiac, aortic, or digestive. An antagonistic relationship between T. cruzi infection and cancer development was also proposed, but the molecular mechanisms involved have remained largely unknown. Probably, a variety of T. cruzi molecules is involved. This review focuses on how T. cruzi calreticulin (TcCRT), exteriorized from the endoplasmic reticulum, targets the first classical complement component C1 and negatively regulates the classical complement activation cascade, promoting parasite infectivity. We propose that this C1-dependent TcCRT-mediated virulence is critical to explain, at least an important part, of the parasite capacity to inhibit tumor development. We will discuss how TcCRT, by directly interacting with venous and arterial endothelial cells, inhibits angiogenesis and tumor growth. Thus, these TcCRT functions not only illustrate T. cruzi interactions with the host immune defensive strategies, but also illustrate a possible co-evolutionary adaptation to privilege a prolonged interaction with its host.

Is it all That Bad When Living with an Intracellular Protozoan? The Role of Trypanosoma cruzi Calreticulin in Angiogenesis and Tumor Growth.

The immune system protects against disease, but may aberrantly silence immunity against "altered self," with consequent development of malignancies. Among the components of the endoplasmic reticulum (ER), important in immunity, is calreticulin (CRT) that, in spite of its residence in the ER, can be translocated to the exterior. Trypanosoma cruzi is the agent of Chagas disease, one of the most important global neglected infections, affecting several hundred thousand people. The syndrome, mainly digestive and circulatory, affects only one-third of those infected. The anti-tumor effects of the infection are known for several decades, but advances in the identification of responsible T. cruzi molecules are scarce. We have shown that T. cruzi CRT (TcCRT) better executes the antiangiogenic and anti-tumor effects of mammal CRT and its N-terminus vasostatin. In this regard, recombinant TcCRT (rTcCRT) and/or its N-terminus inhibit angiogenesis in vitro, ex vivo, and in vivo. TcCRT also inhibits the growth of murine adenocarcinomas and melanomas. Finally, rTcCRT fully reproduces the anti-tumor effect of T. cruzi infection in mice. Thus, we hypothesize that, the long reported anti-tumor effect of T. cruzi infection is mediated at least in part by TcCRT.