Carla Pagliari - Academia.edu (original) (raw)

Papers by Carla Pagliari

Indian Journal of Microbiology

Journal of Medical Virology, Sep 23, 2013

Dengue infection is an important tropical disease worldwide. The host immune response has been st... more Dengue infection is an important tropical disease worldwide. The host immune response has been studied in order to better understand lesion mechanisms. It was performed an immunohistochemical study in 14 specimens of liver from patients with dengue hemorrhagic fever (DHF) to characterize cytokines and some factors present in liver lesions and their possible role in the pathogenesis of hepatic injury. Portal tract and hepatic acinus presented high expression of TLR2, TLR3, IL6, and granzyme B. Hepatic acinus also presented iNOS, IL18, and TGF-beta. Cells expressing IL12, IL13, JAk1, STAT1, and NF-κB were rarely visualized. Treg cells foxp3+ were absent. TLR2 and TLR3 seem to participate in cellular activation and cytokine production. Cytotoxic response seems to play a role. Although TGF-beta promotes the activation of Foxp3+ regulatory T cells, IL6 can significantly suppresses their generation. The expression of Treg cells is diminished probably as a result of the high frequency of these cytokines. Both cytokines play a role in the increased vascular permeability and edema observed in dengue liver specimens, with consequent plasma leakage and severity of the disease. It was observed a regular expression of IL-18 in hepatocytes and lymphocytes of the inflammatory infiltrate in portal tract, which reflects the acute inflammatory response that occurs in the liver and contributes to hepatic injury. At least in part, the increased number of cells expressing IL-18 could play a role of "up" regulation of FasL and correlate to the phenomenon of apoptosis, a mechanism of destruction of hepatocytes in DHF.

Background Cutaneous polyarteritis nodosa (CPAN), a cutaneous vasculitis that affects small-and m... more Background Cutaneous polyarteritis nodosa (CPAN), a cutaneous vasculitis that affects small-and medium-sized arteries, is thought to be mediated by immune complexes. However, little is known about its etiology. Macrophages are important pathogenic factors in various vascular inflammatory diseases, including certain types of vasculitis. However, their role in CPAN remains unexplored. Objectives To describe the demographic, clinical, and laboratory findings and investigate the distribution of M1 and M2 macrophages in CPAN. Methods This was a cross-sectional study involving fourteen patients with CPAN and nine control participants. Medical records were reviewed to determine demographic and clinical data, and laboratory findings. Skin biopsies obtained during disease manifestations were evaluated immunohistochemically. M1 macrophages were identified using STAT1 expression, and M2 macrophages were identified using CD163, CD206, and CMAF expression. Results CPAN was predominant in women, and the mean age of patients was 39 years. The main dermatological lesions were ulcers, subcutaneous nodules, and livedo. Increased lipoprotein(a) levels (28%) and a positive tuberculin skin test in 40% of the tested patients were our main laboratory findings. Direct immunofluorescence was positive in 88.9% of the cases. Immunohistochemical analysis revealed an increased percentage of M2 macrophages in CPAN patients compared with that in the control group. Conclusions This is a novel study on macrophage polarization in CPAN, where the number of cells expressing CD163 and CMAF was found to be increased. M2 macrophage predominance suggests an important role for the innate immune system in the pathophysiology of CPAN and may provide insights for potential therapeutic targets.

Reviews in Medical Virology, Jul 12, 2020

The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) w... more The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous

Biomedicine hub, Jul 25, 2017

Chromoblastomycosis (CBM) is a chronic fungal infection that affects skin and subcutaneous tissue... more Chromoblastomycosis (CBM) is a chronic fungal infection that affects skin and subcutaneous tissue, and little is known about the immunological aspects of such lesions. We have previously described the high expression of IL-17 in this group. Understanding the innate immune response of patients with CBM would improve the knowledge of its immunopathogenesis and contribute to the most appropriate therapies. Nineteen biopsies of verrucous form were obtained from patients with clinical and histopathological diagnosis of CBM, without treatment. This was done with a double immunostaining with conventional immunohistochemistry and immunofluorescence technique as well as confocal microscopy to detect Langerin and IL-17 expression. All of the specimens that were analyzed showed expression of Langerin in the epidermis-the same as the control group. However, only the CBM group presented cells expressing CD207 in the dermis. Interestingly, the coexpression of IL-17 and Langerin was visualized along the epidermis and dermis in 100% of the lesion group. We demonstrated for the

Revista Da Sociedade Brasileira De Medicina Tropical, 2019

Introduction: Dengue is an important mosquito-borne disease in tropical and subtropical regions. ... more Introduction: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. Methods: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. Results: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. Conclusions: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

Brazilian Journal of Infectious Diseases, 2005

Revista Do Instituto De Medicina Tropical De Sao Paulo, 1991

Brazilian Journal of Infectious Diseases, 1999

Revista Do Instituto De Medicina Tropical De Sao Paulo, 1989

JAAD case reports, Sep 1, 2020

Frontiers in Immunology, 2019

Objectives: To compare microscopic and immunologic features in the spleens of patients who died o... more Objectives: To compare microscopic and immunologic features in the spleens of patients who died of pulmonary hemorrhage and shock caused by leptospirosis (11 cases) or Gram-positive/-negative bacterial septic shock (10 cases) to those from control spleens (12 cases from splenectomy). Methodology: Histological features in the red pulp and white pulp were analyzed using archived samples by a semi quantitative score. Immunohistochemistry was used for the recognition of immune cell markers, cytokines, caspase-3 and Leptospira antigens. Results: The control group differed significantly from the leptospirosis and septic shock patients which demonstrate strong similarities: diffuse congestion in the red pulp with a moderate to intense infiltration of plasma cells and polymorphonuclear cells; follicles with marked atrophy; high density of CD20 + cells; low density of NK, TCD4 + and active caspase-3 positive cells and strong expression of IL-10; leptospirosis patients had higher S100 and TNF-α positive cells in the spleen than the other groups. Conclusion: The results suggest that an immunosuppressive state develops at the terminal stage of severe leptospirosis with pulmonary hemorrhage and shock similar to that of patients with septic shock, with diffuse endothelial activation in the spleen, splenitis, and signs of disturbance in the innate and adaptive immunity in the spleen. The presence of leptospiral antigens in 73% of the spleens of the leptospirosis patients suggests the etiological agent contributes directly to the pathogenesis of the lesions. Our results support therapeutic approaches involving antibiotic and immunomodulatory treatments for leptospirosis patients and suggest that leptospirosis patients, which are usually young men with no co-morbidities, form a good group for studying sepsis and septic shock.

Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) ... more Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) presenting wide global dissemination and the pathogenic profile developed in infected individuals, which develop from nonspecific clinical conditions to severe forms, characterized by the promotion of significant lesions in different organs of the harborer, culminating in multiple organ dysfunction. To characterize, quantify, and compare the patterns of histopathological alterations in human liver samples from patients with yellow fever (YF), dengue fever (DF), and chikungunya fever (CF). Analytical cross-sectional study by histopathological analysis with 70 samples of liver patients, collected from 2000 to 2017, with confirmed laboratory diagnosis who died due to infection and complications by the YF, DF, and CF. Of the histopathological findings in human liver samples there was a significant difference between the control and infection groups, with a predominance of alterations in the ...

Sociedade Brasileira de Medicina Tropical, 2003

Sociedade Brasileira de Medicina Tropical, 2003

Indian Journal of Microbiology

Journal of Medical Virology, Sep 23, 2013

Dengue infection is an important tropical disease worldwide. The host immune response has been st... more Dengue infection is an important tropical disease worldwide. The host immune response has been studied in order to better understand lesion mechanisms. It was performed an immunohistochemical study in 14 specimens of liver from patients with dengue hemorrhagic fever (DHF) to characterize cytokines and some factors present in liver lesions and their possible role in the pathogenesis of hepatic injury. Portal tract and hepatic acinus presented high expression of TLR2, TLR3, IL6, and granzyme B. Hepatic acinus also presented iNOS, IL18, and TGF-beta. Cells expressing IL12, IL13, JAk1, STAT1, and NF-κB were rarely visualized. Treg cells foxp3+ were absent. TLR2 and TLR3 seem to participate in cellular activation and cytokine production. Cytotoxic response seems to play a role. Although TGF-beta promotes the activation of Foxp3+ regulatory T cells, IL6 can significantly suppresses their generation. The expression of Treg cells is diminished probably as a result of the high frequency of these cytokines. Both cytokines play a role in the increased vascular permeability and edema observed in dengue liver specimens, with consequent plasma leakage and severity of the disease. It was observed a regular expression of IL-18 in hepatocytes and lymphocytes of the inflammatory infiltrate in portal tract, which reflects the acute inflammatory response that occurs in the liver and contributes to hepatic injury. At least in part, the increased number of cells expressing IL-18 could play a role of "up" regulation of FasL and correlate to the phenomenon of apoptosis, a mechanism of destruction of hepatocytes in DHF.

Background Cutaneous polyarteritis nodosa (CPAN), a cutaneous vasculitis that affects small-and m... more Background Cutaneous polyarteritis nodosa (CPAN), a cutaneous vasculitis that affects small-and medium-sized arteries, is thought to be mediated by immune complexes. However, little is known about its etiology. Macrophages are important pathogenic factors in various vascular inflammatory diseases, including certain types of vasculitis. However, their role in CPAN remains unexplored. Objectives To describe the demographic, clinical, and laboratory findings and investigate the distribution of M1 and M2 macrophages in CPAN. Methods This was a cross-sectional study involving fourteen patients with CPAN and nine control participants. Medical records were reviewed to determine demographic and clinical data, and laboratory findings. Skin biopsies obtained during disease manifestations were evaluated immunohistochemically. M1 macrophages were identified using STAT1 expression, and M2 macrophages were identified using CD163, CD206, and CMAF expression. Results CPAN was predominant in women, and the mean age of patients was 39 years. The main dermatological lesions were ulcers, subcutaneous nodules, and livedo. Increased lipoprotein(a) levels (28%) and a positive tuberculin skin test in 40% of the tested patients were our main laboratory findings. Direct immunofluorescence was positive in 88.9% of the cases. Immunohistochemical analysis revealed an increased percentage of M2 macrophages in CPAN patients compared with that in the control group. Conclusions This is a novel study on macrophage polarization in CPAN, where the number of cells expressing CD163 and CMAF was found to be increased. M2 macrophage predominance suggests an important role for the innate immune system in the pathophysiology of CPAN and may provide insights for potential therapeutic targets.

Reviews in Medical Virology, Jul 12, 2020

The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) w... more The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous

Biomedicine hub, Jul 25, 2017

Chromoblastomycosis (CBM) is a chronic fungal infection that affects skin and subcutaneous tissue... more Chromoblastomycosis (CBM) is a chronic fungal infection that affects skin and subcutaneous tissue, and little is known about the immunological aspects of such lesions. We have previously described the high expression of IL-17 in this group. Understanding the innate immune response of patients with CBM would improve the knowledge of its immunopathogenesis and contribute to the most appropriate therapies. Nineteen biopsies of verrucous form were obtained from patients with clinical and histopathological diagnosis of CBM, without treatment. This was done with a double immunostaining with conventional immunohistochemistry and immunofluorescence technique as well as confocal microscopy to detect Langerin and IL-17 expression. All of the specimens that were analyzed showed expression of Langerin in the epidermis-the same as the control group. However, only the CBM group presented cells expressing CD207 in the dermis. Interestingly, the coexpression of IL-17 and Langerin was visualized along the epidermis and dermis in 100% of the lesion group. We demonstrated for the

Revista Da Sociedade Brasileira De Medicina Tropical, 2019

Introduction: Dengue is an important mosquito-borne disease in tropical and subtropical regions. ... more Introduction: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. Methods: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. Results: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. Conclusions: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

Brazilian Journal of Infectious Diseases, 2005

Revista Do Instituto De Medicina Tropical De Sao Paulo, 1991

Brazilian Journal of Infectious Diseases, 1999

Revista Do Instituto De Medicina Tropical De Sao Paulo, 1989

JAAD case reports, Sep 1, 2020

Frontiers in Immunology, 2019

Objectives: To compare microscopic and immunologic features in the spleens of patients who died o... more Objectives: To compare microscopic and immunologic features in the spleens of patients who died of pulmonary hemorrhage and shock caused by leptospirosis (11 cases) or Gram-positive/-negative bacterial septic shock (10 cases) to those from control spleens (12 cases from splenectomy). Methodology: Histological features in the red pulp and white pulp were analyzed using archived samples by a semi quantitative score. Immunohistochemistry was used for the recognition of immune cell markers, cytokines, caspase-3 and Leptospira antigens. Results: The control group differed significantly from the leptospirosis and septic shock patients which demonstrate strong similarities: diffuse congestion in the red pulp with a moderate to intense infiltration of plasma cells and polymorphonuclear cells; follicles with marked atrophy; high density of CD20 + cells; low density of NK, TCD4 + and active caspase-3 positive cells and strong expression of IL-10; leptospirosis patients had higher S100 and TNF-α positive cells in the spleen than the other groups. Conclusion: The results suggest that an immunosuppressive state develops at the terminal stage of severe leptospirosis with pulmonary hemorrhage and shock similar to that of patients with septic shock, with diffuse endothelial activation in the spleen, splenitis, and signs of disturbance in the innate and adaptive immunity in the spleen. The presence of leptospiral antigens in 73% of the spleens of the leptospirosis patients suggests the etiological agent contributes directly to the pathogenesis of the lesions. Our results support therapeutic approaches involving antibiotic and immunomodulatory treatments for leptospirosis patients and suggest that leptospirosis patients, which are usually young men with no co-morbidities, form a good group for studying sepsis and septic shock.

Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) ... more Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) presenting wide global dissemination and the pathogenic profile developed in infected individuals, which develop from nonspecific clinical conditions to severe forms, characterized by the promotion of significant lesions in different organs of the harborer, culminating in multiple organ dysfunction. To characterize, quantify, and compare the patterns of histopathological alterations in human liver samples from patients with yellow fever (YF), dengue fever (DF), and chikungunya fever (CF). Analytical cross-sectional study by histopathological analysis with 70 samples of liver patients, collected from 2000 to 2017, with confirmed laboratory diagnosis who died due to infection and complications by the YF, DF, and CF. Of the histopathological findings in human liver samples there was a significant difference between the control and infection groups, with a predominance of alterations in the ...

Sociedade Brasileira de Medicina Tropical, 2003

Sociedade Brasileira de Medicina Tropical, 2003