Interleukin-10-dependent down-regulation of interferon-gamma response to Leishmania by Mycobacterium leprae antigens during the clinical course of a coinfection

Azeredo-Coutinho, Rilza Beatriz; Matos, Denise C. S.; Nery, José A. C.; Valete‐Rosalino, Cláudia Maria; Mendonça, Sergio C. F.

doi:10.1590/s0100-879x2012007500073

Cited by 14 publications

(16 citation statements)

References 21 publications

(34 reference statements)

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“…We found descriptions of five patients with lepromatous leprosy and localised TL [ 74 , 75 , 77 – 79 ]. In one of these cases, a man with lepromatous leprosy and mucosal leishmaniasis, skin reaction and IFNγ production against Leishmania antigens were strong, whereas the responses against M .…”

Section: Resultsmentioning

confidence: 99%

Tegumentary leishmaniasis and coinfections other than HIV

et al. 2018

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BackgroundTegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by Leishmania parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.Methodology and principal findingsThis review focuses on the frequency of TL coinfections in human populations, interactions between Leishmania and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of Trypanosoma cruzi coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., Leishmania and Sporothrix schenckii), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.Conclusions and significanceIn patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.

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Section: Resultsmentioning

confidence: 99%

Tegumentary leishmaniasis and coinfections other than HIV

et al. 2018

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“…40 Interactions between M. leprae and Leishmania may occur, as during active leprosy, M. leprae antigens can induce an IL-10-mediated regulatory response that controls the immunopathology of L. braziliensis-induced mucosal leishmaniasis. 41 In addition, the colocation of M. leprae with Leishmania spp. in biopsies is especially intriguing.…”

Section: Discussionmentioning

confidence: 99%

Leprosy Associated with Atypical Cutaneous Leishmaniasis in Nicaragua and Honduras

Soto

Caballero

Fuentes³

et al. 2017

The American Journal of Tropical Medicine and Hygiene

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In Central America, few cases of leprosy have been reported, but the disease may be unrecognized. Diagnosis is based on clinical criteria and histology. Preliminary field work in Nicaragua and Honduras found patients, including many children, with skin lesions clinically suggestive of atypical cutaneous leishmaniasis or indeterminate leprosy. Histology could not distinguish these diseases although acid-fast organisms were visible in a few biopsies. Lesions healed after standard antimicrobial therapy for leprosy. In the present study, patients, family members, and other community members were skin-tested and provided nasal swabs and blood samples. Biopsies were taken from a subgroup of patients with clinical signs of infection. Two laboratories analyzed samples, using local in-house techniques. , spp. and were detected using polymerase chain reactions. DNA was detected in blood samples and nasal swabs, including some cases where leprosy was not clinically suspected. spp. were also detected in blood and nasal swabs. Most biopsies contained DNA and coinfection of spp. with occurred in 33% of cases. DNA was also detected and sequenced from Nicaraguan and Honduran environmental samples. In conclusion, leprosy and leishmaniasis are present in both regions, and leprosy appears to be widespread. The nature of any relationship between these two pathogens and the epidemiology of these infections need to be elucidated.

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“…The level of IFN‐γ may affect the amount of IL‐10 production 39 and inversely, the level of IL‐10 can affect the amount of IFN‐γ secreted 40 . Therefore, the lower IFN‐γ produced during a young mouse's response to infection may or may not be influence the amount of IL‐10 produced.…”

Section: Discussionmentioning

confidence: 99%

“…The level of IFN-γ may affect the amount of IL-10 production 39 and inversely, the level of IL-10 can affect the amount of IFN-γ secreted. 40 Therefore, the lower IFN-γ produced during a young mouse's response to infection may or may not be influence the amount of IL-10 produced. In contrast to another study in adult mice, 21 we did not find low IL-10 levels in the lungs during infection affected the levels of IL-17a production (data not shown) nor did we find an influence on IFN-γ levels.…”

Section: Discussionmentioning

confidence: 99%

Differential mucosal IL‐10‐induced immunoregulation of innate immune responses occurs in influenza infected infants/toddlers and adults

Verhoeven

Perry

2016

Immunol Cell Biol

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Young children (<5 years of age but especially those <2-year old) exhibit high rates of morbidity and frequently require hospitalizations due to complications from respiratory viral infections. This is also a population for which we understand less about how their unique level of immunological maturation affects their antiviral immune responses. However, we do know from prior studies that their T cells appear to apoptose in the lungs owing to limited interferon (IFN)γ autocrine signaling during infection. To begin to further understand additional limits, we utilized an infant/toddler murine model infected with influenza virus with an adult comparator. In our model, young mice exhibited lower interleukin (IL)-10IFNγ co-producing CD4 T cells infiltrating the lungs that paralleled with a failed switch from an innate to adaptive immune response at the mid infection stage. Specifically, limited co-IL-10 production correlated with a lack of influenza-specific antibodies and subsequent complement receptor signaling (complement receptor type-1 related gene Y (CCRY)/p65) to the lung infiltrating CD4 T cells therefore limiting their IKAROs upregulation. Thus, limited IL-10 production appeared to diminish signaling to lung macrophages to stop accumulating late into infection. Taken together, our results suggest a novel role for complement mediated signaling in CD4 T cells with respect to IL-10 co-production. Furthermore, a subsequent failure to shift from the unfocused innate immune response to the specific adaptive responses may be a principle cause in the enhanced morbidity common in respiratory viral infection of young children.

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Interleukin-10-dependent down-regulation of interferon-gamma response to Leishmania by Mycobacterium leprae antigens during the clinical course of a coinfection

Cited by 14 publications

References 21 publications

Tegumentary leishmaniasis and coinfections other than HIV

Tegumentary leishmaniasis and coinfections other than HIV

Leprosy Associated with Atypical Cutaneous Leishmaniasis in Nicaragua and Honduras

Differential mucosal IL‐10‐induced immunoregulation of innate immune responses occurs in influenza infected infants/toddlers and adults

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