Immunology Case Reports

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Review Article - Immunology Case Reports (2017) Volume 1, Issue 2

Harnessing the Immune Regulatory Balance of Toll-like Receptor 9 Agonists in Cancer Immunotherapy.

Brasileiro MR*

Bachelor of Biological Sciences and Master of Animal Science Universidade do Oeste Paulista, UNOESTE, Brazil

*Corresponding Author:
Brasileiro MR
Bachelor of Biological Sciences and Master of Animal Science
Universidade do Oeste Paulista UNOESTE
Tel: 18998138768

Accepted date: June 3, 2017


Toll-like receptor 9 (TLR9), a naturally existing immune regulatory site, not only takes part in enhancing anti-tumor immunity but also promoting the immunosuppressive environment of the growing tumor. TLR9 has shown its potential activity as a therapeutic target in cancer immunotherapy. However, the increased pro-tumor inflammation mediated by TLR9 should also be considered. Therefore, it is important to develop a better understanding of its regulatory mechanisms to improve the therapeutic efficacy. This review will discuss the mechanisms of immune homeostasis regulated by TLR9 signaling pathways, and also introduce the strategies of how to harness the immune regulatory balance by TLR9 agonists, CpG oligodeoxynucleotides, in cancer immunotherapies.


Chagas disease, American trypanosomiasis, Trypanosoma cruzi, Parasitic zoonosis.


Carlos Chagas, on a mission to control the outbreak of malaria in workers of the Central Railway of Brazil in 1907, became aware of a hematophagous insect, commonly known as a "barbeiro", which was described as a vector of the protozoan Trypanosoma cruzi (CHAGAS). Since then, studies have focused on the discovery of the infectious-contaminant aspects, control, way of life and other species of vectors and parasites that cause Chagas Disease. The causative agent of Chagas disease, T. cruzi flagellate protozoan belongs to the order Kinetoplastida, family Trypanosomatidae. Unlike other diseases transmitted by hematophagous vectors, the transmission does not occur by the inoculation of the agent with saliva but by the sting, followed by defecation in the act or after hematophagy, such feces contain infective forms of the parasite, which penetrate both in Wounds and mucous membranes, as well as through the bite hole of the vector itself [1]. Acute Chagas disease (ACD) or American trypanosomiasis is a unique anthropozoonosis in the Americas, representing the fourth major social impact among infectious and parasitic diseases in Latin America [2]. The vector transmission depends on three basic factors, being the presence of T. cruzi, domiciled triatomines and mammalian hosts in the home environment. This form of infection, called classical, affects 80% of infections, being directly linked to human factor and socioeconomic conditions [3]. Another route of infection is through blood transfusion, transplacental and organ transplantation, both of which involve an infected patient, and may also occur by accidental ingestion of triatomines or feces of the infected insect.


The "barber" is an arthropod of the class insecta, order hemiptera, family reduviidae and subfamily triatominae that feeds exclusively on homeothermic vertebrates, being called hematophagous. They are usually sheltered in a place very close to the source of food and can be found in the forest in birds' nests, animal scarf, tree trunk bark, wood fences and under stones, present average life between one and two years, With evolution of egg, nymph and adult. They have a great breeding capacity and, depending on the species, intense resistance to fasting.

Life cycle

Eggs: The female copulates once and after about 20 to 30 days begins the posture. Each female oviposes about 200 eggs. Egg hatching occurs on average 25 days after laying.

Nymphs: Eggs hatch into nymphs, which seek food 2 or 3 days after birth. After your first meal the nymph will suffer loss of your skin. The "barber" goes through 5 seedlings until reaching the adult stage.

Adults: The adult lives for a few months, reaching a year or more. The females do the first posture with about 2 months. After laying, they tend to migrate and form new colonies. The life cycle lasts on average from 1 to 2 years.

Ecological distribution of triatomines

A total 118 species of triatomines are known, and 105 are from the New World, both potential vectors for T. cruzi, being the most important vector in north-eastern Brazil, frequently found in wild and peridomiciliary habitats, where is strongly associated with shelters of goats, chickens and rocky ecotypes, and in the home environment it has birds and humans as the main food source.

Clinic and Diagnosis

The acute form of the disease usually occurs in children, with the presence of late chronic manifestations. The clinical manifestations are rare, being characterized by fever of variable intensity, malaise, lymphadenopathy and hepatosplenomegaly. Diagnosis in the acute phase is established by demonstration of the parasite through blood, culture or immunodiagnostic screening.


Due to the infection transmission cycle, the control measures are generally directed to the control of the vector through chemical and biological control, and quality control of the blood transfused through the supervision of hemotherapy units in the control of quality of blood to be transfused through the serological screening of all blood donors with at least two sensitivity techniques. The main objective was to explain the epidemiological situation of Chagas' disease in Brazil from 2001 to 2014, resulting in the quantification of confirmed cases in the regions and identification of the regions with the highest percentage of cases.

Materials and Methods

The research was carried out without the approval of the Ethics Chamber in Animal Experimentation (CEUA), since it did not evaluate the use of animals, but rather a platform of the Ministry of Health / SVS-Information System of Notification Aggravations-SINAN online that allows the collection of tabulated and revised information [4]. With the collection of data on the platform, it was possible to identify the number of total cases in each year and each federative unit (UF), thus presenting the percentage of cases of the disease in the given period.

Results and Discussion

The Brazilian regions most affected by the disease were Northeast (42.5%) and North (41.3%), as shown in Table 1. Regarding the incidence of cases, it can be observed that in the period from 2001 to 2007 the Northeast region presented the highest number of cases in the country, and in the period from 2005 to 2014 there was a significant decrease in the number of cases in the region, which suggests a positive impact of control and awareness measures, supposedly adopted by the public health organs.

Ano/Região Norte Nordeste Sudeste Sul Centro-Oeste Total/Ano
2001 5 37 7 12 0 61
2002 38 114 36 48 10 246
2003 49 436 33 46 15 579
2004 38 264 42 58 17 419
2005 52 426 57 78 16 629
2006 132 299 44 45 24 544
2007 151 3 0 0 1 155
2008 96 8 0 0 0 104
2009 214 5 0 0 1 220
2010 104 10 0 1 15 130
2011 166 16 0 0 8 190
2012 186 2 0 1 0 189
2013 157 2 2 1 1 163
2014 192 3 1 1 1 198
Total de Casos
1580 (41.3%) 1625
Média de casos 113/ano 116/ano 16/ano 21/ano 8/ano 273/ano

Table 1. Number of confirmed cases for ACD in Brazil - 2001-2014.

Chagas disease is one of the main tropical diseases, its transmission is relatively simple, and having a wide variety of mammalian vectors and hosts. Knowing that vectors are included in the peridomiciliary environment, occupying areas of human activity, this fulfils the three requirements described by Dias in front of the line of infection and transmission. Since prevention and control measures adopted in the Northeast region during the period 2005 to 2014 have supposedly had a significant effect in relation to the number of cases, it is consistent with epidemiological research, with emphasis on both the quantitative description of cases and to monitor the evolution of the disease in the country [5,6].


It was observed a high incidence in the number of cases of the Brazilian North region in relation to the other regions, which verified the second place in the total of cases of the country. On the other hand, there was significant control in the incidence of cases in other regions of the country over the years, mainly in the Northeast region. This suggests that measures of control and awareness applied to the population are essential for the prevention and combat of the disease.


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