Mycobacterium tuberculosisUpregulates Coreceptors CCR5 and CXCR4 While HIV Modulates CD14 Favoring Concurrent Infection

Abstract

Tuberculosis is the most frequent coinfection in humans infected with HIV-1, but little is known about mechanisms that favors coinfection. The aim of this work is to understand tuberculosis and HIV infections. We determined the pattern of expression of CD11c, CD14, CD40, CCR5, and CXCR4 and quantified IL-1beta, IL-6, IL-8, TNF-alpha, and RANTES in tuberculosis patients and HIV patients. Monocytes from healthy PPD+ volunteers (HP(+)V) stimulated with intracellular proteins (IP), lipids, and polysaccharides (PLS) from Mycobacterium tuberculosis down regulate CD11c expression (p < 0.05). On the contrary, CD14 expression was elevated in tuberculosis patients (p < 0.05) and HIV-infected patients (p > 0.05). CD14 expression was elevated on monocytes from HP(+)V stimulated with PLS and lipids (p < 0.05). CD40 low expression was found in tuberculosis patients and on monocytes from HP(+)V stimulated with lipids, but it was elevated in HIV-infected patients (p < 0.05). CXCR4 and CCR5 expression was high in pulmonary tuberculosis patients and low in HIV-infected patients (p < 0.05). Finally, CCR5+ monocytes from HP(+)V after stimulation with PLS and CXCR4+ lymphocytes were elevated after stimulation with IP (p < 0.05). In general, high levels of IL-1beta, IL-6, and TNF-alpha were found in all groups, but low levels of RANTES were found in pulmonary tuberculosis patients. In conclusion, the pulmonary tuberculosis patients have a microenvironment that facilitates the HIV infection through three possible mechanisms: (1) increasing the coreceptor for HIV entrance, (2) increasing proinflammatory cytokines, and (3) down-regulating RANTES. At the same time, HIV patients have a microenvironment that facilitates entry of M. tuberculosis into macrophages through CD14.

Tuberculosis and HIV Co-Infection

“…There is also some evidence that CD8 + T cells play a role in the control of latent TB [41]–[44]. Other mechanisms reported to facilitate M. tuberculosis infection and disease in individuals with HIV are up-regulation of M. tuberculosis entry receptors on macrophages [45], HIV manipulation of macrophage bactericidal pathways [46], deregulated chemotaxis [47], and a tipped Th1/Th2 balance [48]. It has also been shown that HIV impairs tumor necrosis factor (TNF)-mediated macrophage apoptotic response to M. tuberculosis and thus facilitates bacterial survival [49].…”

“…Furthermore, monocytes from HIV + patients display an impaired response to TLR ligands [74], and viral proteins can interfere with both MDM and DC maturation and function in vitro, including their ability to phagocytose mycobacteria and kill intracellular bacteria [75]–[78]. SOCS1, which is stimulated by infection with M. tuberculosis [45], has been shown to facilitate the late replication pathways of HIV infection [79] and mediate viral evasion of type I IFN anti-viral signalling [80].…”

Tuberculosis and HIV Coinfection: Table 1.

“…In vitro studies have shown that M. tuberculosis infection can increase both HIV infection and replication within macrophages and the efficiency of virus transmission from infected macrophages to T cells (Mancino et al 1997). Upregulation of the coreceptors CXCR4 and CCR5 (Hoshino et al 2004;Rosas-Taraco et al 2006), SOCS1, which is stimulated by infection with M. tuberculosis (Rosas-Taraco et al 2006), has been shown to facilitate the late replication pathways of HIV infection (Ryo et al 2008) and mediate viral evasion of type-1 IFN antiviral signaling (Fenner et al 2006). The transcription factors NF-kB and NFAT5 are required for M. tuberculosis -induced HIV-1 replication in macrophages (Ranjbar et al 2012).…”

Prévalence de la co-infection VIH-tuberculose et impact de l’infection VIH sur l’évolution de la tuberculose pulmonaire au Togo

“…Concernant le VIH, le nombre de personnes vivant avec le VIH (PVVIH) en ASS a été estimé en 2007 à 22,5 millions, soit 68 % de la prévalence mondiale [8]. L'infection à VIH favorise la réactivation d'une infection latente à M. tuberculosis vers une TB maladie et M. tuberculosis favorise la réplication du VIH et accélère ainsi l'évolution naturelle de l'infection vers une immunodépression [10,13]. Ainsi, la TB est la première cause d'infection opportuniste et de décès chez les PVVIH en Afrique au sud du Sahara [5] et un patient infecté par le VIH a un risque élevé de déve-lopper une TB active dans un pays à forte incidence de la TB [16].…”