Resident synovial macrophages in synovial fluid: Implications for immunoregulation.

Resident synovial macrophages (RSMs) are anti-inflammatory, self-renewing macrophages that provide physical immune sequestration of the joint space from the peripheral immune system. Increased permeability of this structure is associated with peripheral immune cells in the synovial fluid (SF). Direct measures of synovial barrier integrity are possible with tissue histology, but after barrier breakdown, if these cells perpetuate or initiate chronic inflammation in SF remains unknown.

Dogs as Reservoirs for Leishmania donovani, Bihar, India, 2018-2022.

Visceral leishmaniasis derived from Leishmania donovani is transmitted by sand flies (Phlebotomus argentipes) throughout the Indian subcontinent. Although considered anthroponotic, L. donovani infects other mammals susceptible to sand fly bites, including dogs.

Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection.

The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease.

Joint Bayesian longitudinal models for mixed outcome types and associated model selection techniques.

Motivated by data measuring progression of leishmaniosis in a cohort of US dogs, we develop a Bayesian longitudinal model with autoregressive errors to jointly analyze ordinal and continuous outcomes. Multivariate methods can borrow strength across responses and may produce improved longitudinal forecasts of disease progression over univariate methods. We explore the performance of our proposed model under simulation, and demonstrate that it has improved prediction accuracy over traditional Bayesian hierarchical models.

Resident Synovial Macrophages in Synovial Fluid: Implications for Immunoregulation in Infectious and Inflammatory Arthritis.

Objectives: Resident synovial macrophages (RSM) provide immune sequestration of the joint space and are likely involved in initiation and perpetuation of the joint-specific immune response. We sought to identify RSM in synovial fluid (SF) and demonstrate migratory ability, in additional to functional changes that may perpetuate a chronic inflammatory response within joint spaces.

Methods: We recruited human patients presenting with undifferentiated arthritis in multiple clinical settings.

Modulation of Macrophage Redox and Apoptotic Processes to during Coinfection with the Tick-Borne Bacteria .

Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan . Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including in the United States. These coinfections have been causally associated with hastened disease progression and mortality.

Within-Host Bayesian Joint Modeling of Longitudinal and Time-to-Event Data of Infection.

The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease.

Bayesian multivariate longitudinal model for immune responses to Leishmania: A tick-borne co-infection study.

While many Bayesian state-space models for infectious disease processes focus on population infection dynamics (eg, compartmental models), in this work we examine the evolution of infection processes and the complexities of the immune responses within the host using these techniques. We present a joint Bayesian state-space model to better understand how the immune system contributes to the control of Leishmania infantum infections over the disease course. We use longitudinal molecular diagnostic and clinical data of a cohort of dogs to describe population progression rates and present evidence for important drivers of clinical disease.

NLRP12-expressing dendritic cells mediate both dissemination of infection and adaptive immune responses in visceral leishmaniasis.

The NLR protein NLRP12 contributes to innate immunity, but the mechanism remains elusive. Infection of or wild-type mice with led to aberrant parasite tropism. Parasites replicated to higher levels in livers of mice than in the livers of WT mice and failed to disseminate to spleens.

Livestock and rodents within an endemic focus of Visceral Leishmaniasis are not reservoir hosts for Leishmania donovani.

Leishmaniasis on the Indian subcontinent is thought to have an anthroponotic transmission cycle. There is no direct evidence that a mammalian host other than humans can be infected with Leishmania donovani and transmit infection to the sand fly vector. The aim of the present study was to evaluate the impact of sand fly feeding on other domestic species and provide clinical evidence regarding possible non-human reservoirs through experimental sand fly feeding on cows, water buffalo goats and rodents.

Visceral Leishmaniasis and the Skin: Dermal Parasite Transmission to Sand Flies.

Visceral leishmaniasis is a parasitic disease with significant dermal tropism. The skin is an important site of infection contributing to parasite transmission to naïve sand flies, but understanding how parasitism of host skin and the related immune microenvironment supports or prevents skin parasite replication is now the focus of major investigation in the field of leishmaniasis research. Here, we review dermatoimmunology during visceral leishmaniasis (VL), dermal parasite burden, and the role of skin parasitism in transmissibility to sand fly vectors.

Role of NK-Like CD8 T Cells during Asymptomatic Borrelia burgdorferi Infection.

Lyme disease (LD) due to Borrelia burgdorferi is the most prevalent vector-borne disease in the United States. There is a poor understanding of how immunity contributes to bacterial control, pathology, or both during LD. Dogs in an area of endemicity were screened for B.

Bayesian latent class models for identifying canine visceral leishmaniosis using diagnostic tests in the absence of a gold standard.

Background: Like many infectious diseases, there is no practical gold standard for diagnosing clinical visceral leishmaniasis (VL). Latent class modeling has been proposed to estimate a latent gold standard for identifying disease. These proposed models for VL have leveraged information from diagnostic tests with dichotomous serological and PCR assays, but have not employed continuous diagnostic test information.

Epidemiologic, Clinical and Immunological Consequences of Co-Infections during Canine Leishmaniosis.

Canine leishmaniosis (CanL) is a vector-borne, parasitic disease. CanL is endemic in the Mediterranean basin and South America but also found in Northern Africa, Asia, and the U.S.

Leishmania infantum xenodiagnosis from vertically infected dogs reveals significant skin tropism.

Background: Dogs are the primary reservoir for human visceral leishmaniasis due to Leishmania infantum. Phlebotomine sand flies maintain zoonotic transmission of parasites between dogs and humans. A subset of dogs is infected transplacentally during gestation, but at what stage of the clinical spectrum vertically infected dogs contribute to the infected sand fly pool is unknown.

Domestic mammals as reservoirs for Leishmania donovani on the Indian subcontinent: Possibility and consequences on elimination.

Leishmania donovani is the causative agent of historically anthroponotic visceral leishmaniasis (VL) on the Indian subcontinent (ISC). L. donovani is transmitted by the sand fly species Phlebotomus argentipes.

Predominant risk factors for tick-borne co-infections in hunting dogs from the USA.

Background: Both incidence and geographical range of tick-borne disease has increased across the USA. Similar to people, dogs are hosts for Anaplasma spp., Babesia spp.

Bayesian compartmental models and associated reproductive numbers for an infection with multiple transmission modes.

Zoonotic visceral leishmaniasis (ZVL) is a serious neglected tropical disease that is endemic in 98 countries. ZVL is primarily transmitted via a sand fly vector. In the United States, it is enzootic in some canine populations; it is transmitted from infectious mother to pup transplacentally, and vector-borne transmission is absent.

Coinfection with Leishmania major and Staphylococcus aureus enhances the pathologic responses to both microbes through a pathway involving IL-17A.

Cutaneous leishmaniasis (CL) is a parasitic disease causing chronic, ulcerating skin lesions. Most humans infected with the causative Leishmania protozoa are asymptomatic. Leishmania spp.

An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis.

The role of the nucleotide-binding domain and leucine-rich repeat containing receptor NLRP10 in disease is incompletely understood. Using three mouse strains lacking the gene encoding NLRP10, only one of which had a coincidental mutation in DOCK8, we documented a role for NLRP10 as a suppressor of the cutaneous inflammatory response to infection. There was no evidence that the enhanced local inflammation was due to enhanced inflammasome activity.

Differential Activation of Human Keratinocytes by Leishmania Species Causing Localized or Disseminated Disease.

All Leishmania species parasites are introduced into mammalian skin through a sand fly bite, but different species cause distinct clinical outcomes. Mouse studies suggest that early responses are critical determinants of subsequent adaptive immunity in leishmaniasis, yet few studies address the role of keratinocytes, the most abundant cell in the epidermis. We hypothesized that Leishmania infection causes keratinocytes to produce immunomodulatory factors that influence the outcome of infection.

Cutaneous Manifestations of Human and Murine Leishmaniasis.

The leishmaniases are diseases caused by pathogenic protozoan parasites of the genus Infections are initiated when a sand fly vector inoculates parasites into the skin of a mammalian host. causes a spectrum of inflammatory cutaneous disease manifestations. The type of cutaneous pathology is determined in part by the infecting species, but also by a combination of inflammatory and anti-inflammatory host immune response factors resulting in different clinical outcomes.