Positive Correlation between IP-10 and IFN-γLevels in Rhesus Monkeys(Macaca mulatta)with Either Naturally Acquired or Experimental Infection ofMycobacterium tuberculosis

Abstract

Numerous studies identify that IP-10 and IFN-γ are involved in leucocyte migration and activation and regarded as promising surrogate biomarkers in human and bovine tuberculosis infection, but there is lack of evidence for IP-10 in nonhuman primates. In this study, we directly determined IP-10 and IFN-γ levels in plasma from 30 healthy monkeys, 30 monkeys with naturally acquired tuberculosis, 4 monkeys experimentally infected with tuberculosis, and PPD stimulated whole blood of 14 monkeys with naturally acquired tuberculosis by ELISA. Higher plasma levels of IP-10 and IFN-γ were observed in natural tuberculosis monkeys than in healthy controls. The dynamic changes of plasma IP-10 and IFN-γ in experimental infections showed consistent representation of a transient increase during the infection period. After PPD stimulation, release of IP-10 and IFN-γ is significantly induced in natural tuberculosis monkeys, but the stimulation index of IP-10 was significantly lower than IFN-γ. Further analysis showed that positive correlation between IP-10 and IFN-γ existed in healthy and tuberculosis monkeys. Our findings support plasma IP-10 and IFN-γ as biomarkers for monitoring ongoing inflammation of nonhuman primate tuberculosis, and IFN-γ is a more valuable diagnostic biomarker.

DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

“…In the current study, the results revealed highly significant elevation in serum IFN-γ level (Table 1) in newly diagnostic TB patients, relapse TB patients and healthy controls (P<0.001and P<0.014, respectively). These results are consistent with previous studies showing elevated plasma levels of IFN-in newly diagnosed TB patients and relapse TB patients suggesting up-regulation in the proinflammatory response (18,19).…”

“…The fact that serum IFN-γ levels are up-regulated in the newly diagnosed TB patients indicates innate protective response during early phase of M. tuberculosis infection. The results of the current study agree with previous studies (19)(20)(21)(22)(23).These findings could be referred to possibility of developing immune-prognostic assays based on new biomarkers detection.…”

“…Pro-inflammatory cytokines including IFN-γ are produced from activated macrophages as response to toll like receptor-2(TLR-2) signaling pathway. In active tuberculosis, serum levels of these mediators and IFN-γ levels have been proved high in patients (11).Interferon gamma is one of the most important pro-inflammatory cytokines in many infectious or noninfectious chronic inflammatory diseases, and whole blood IFNassays are popular in diagnosis of human tuberculosis (17,18,19). In the current study, the results revealed highly significant elevation in serum IFN-γ level (Table 1) in newly diagnostic TB patients, relapse TB patients and healthy controls (P<0.001and P<0.014, respectively).…”

In vitro responses of multiple cytokines to purified protein derivative in healthy and naturally Mycobacterium tuberculosis‐infected rhesus monkeys (Macaca mulatta)

“…14,[17][18][19] This study aimed to evaluate more cytokines as alternative biomarkers of whole-blood stimulation assays in diagnosing nonhuman Panel 1 6 TNF RII, IL19, RANTES, MIF, MPO, Galectin-3 Panel 2 37 IFN-γ, TNF-α, TNF RI, GM-CSF, IL1β, IL1RA, IL1 RII, IL2, IL2 Rα, IL4, IL5, IL6, IL6 Rα, IL8, IL10, IL15, IL17A, IL22, MCP-1, MIP-1β, MCP-3, MCP-4, CCL11, CCL18, CCL22, CCL27, CXCL1, CXCL4, IP-10, CXCL12, CXCL13, CD14, CD27, CD30 been proven to be robust biomarkers of whole-blood stimulation assays. [22][23][24] In our study, IFN-γ and IP-10 were also identified as sensitive markers for the PPD-based whole-blood stimulation assay in nonhuman primates, and IP-10 appeared to be more sensitive than…”

Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses

“…With live bacterial vaccine/infection, functional antagonistic co-regulation of the observed response by Th17 and Treg cells is likely to occur-an area for future investigation. Both DVC and USAMRIID-LVS also induced production of the cytokines IFN-γ and IP-10, which are known to be regulators of activated T lymphocytes and have been suggested as potential biomarkers for other bacterial infections such as M. tuberculosis [43].…”